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The July issue of ONCOLOGY features a review article on immune modulation in sarcoma, plus insights on double lung transplant, the FDA approval of taletrectinib, and utilizing oncodermatology. 

July ONCOLOGY Publication

Of patients who underwent urgent or emergent CRC surgery, 64.4% had open surgery, 31.9% underwent laparoscopic procedures, and 3.7% had robotic surgery.

Among select patients undergoing surgery for colorectal cancer (CRC), robotic surgery conferred lower conversion rates to open surgery and fewer surgical complications compared to laparoscopy, according to results from a retrospective analysis published in the 

Journal of the American College of Surgeons.

Specifically, among 83,483 patients who underwent urgent or emergent colorectal surgery, surgical complications were significantly lower among patients treated with robotic surgery vs laparoscopy (OR, 0.65; 95% CI, 0.60-072; 

<.001). Additionally, open surgery was associated with an increased risk of surgical complications compared to laparoscopy (OR, 2.04; 95% CI, 1.97-2.12; 

<.001). Furthermore, the strongest predictors of surgical complication rates included American Surgical Association (ASA) class 4 to 5 (OR, 2.43; 95% CI, 2.30-2.57), septic shock (OR, 10.88; 95% CI, 9.69-12.21), and total functional dependence (OR, 1.62; 95% CI, 1.42-1.85).

Robotic surgery showed a lower risk of medical complications compared with laparoscopy (OR, 0.79; 95% CI, 0.68-0.93; 

= .005). Compared with laparoscopy, open surgery was associated with a higher risk of medical complications (OR, 1.62; 95% CI, 1.54-1.70; 

<.001). ASA class 4 to 5 (OR, 4.02; 95% CI, 3.74-4.31) and septic shock (OR, 5.53; 95% CI, 5.16-5.94) were also both strong predictors of medical complications, as well as colitis (OR, 1.53; 95% CI, 1.34-1.75).

Further findings revealed that the unadjusted conversion rate to open surgery between robotic vs laparoscopic cases was 7.8% vs 24.2%. This difference was significant across analytical approaches, including multivariable logistic regression (OR, 0.32; 95% CI, 0.28-0.36; 

<.001), propensity score matching (OR, 0.21; 95% CI, 0.18-0.25; 

<.001), and g-computation analysis (OR, 0.34; 95% CI, 0.29-0.38; 

“Robotic surgery represents a viable and advantageous approach for emergency colorectal surgery, with lower conversion rates to open surgery and improved postoperative outcomes compared to both laparoscopic and open approaches,” lead author Davide Ferrari, MD, general surgery resident in the Division of Colon and Rectal Surgery of the Department of Surgery at Mayo Clinic, wrote in the publication with study coinvestigators. “While patient selection remains important, our findings indicate that the technical advantages of the robotic platform persist even in more complex cases, suggesting broader applicability than previously considered. The projected increase in robotic utilization to 20.2% of emergency colorectal procedures by 2025 reflects the growing acceptance of this technology.”

Patient data in the retrospective study were collected from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Risk-adjusted data were gathered from medical charts and included an assessment of a patient’s condition 30 days after a surgical procedure. A random sample of about 20% of the total cases formed the final dataset.

Those who underwent open, laparoscopic, or robotic colectomy in the “Targeted Colectomy” file within the ACS-NSQIP were included in the study, with data ranging from January 2012 to December 2021.

Of patients who underwent urgent or emergent CRC surgery, 64.4% had open surgery, 31.9% underwent laparoscopic procedures, and 3.7% had robotic surgery. Notable characteristic differences included a higher proportion of White (81.6%) and obese patients (41.6%), classified as a BMI of greater than 30 kg/m

, among those who underwent robotic surgery. A lower proportion of patients older than 80 years (6.1%) were selected for a robotic procedure.

The primary end points of the study were overall complications, medical and surgical complications, conversion rate to open surgery, and length of hospital stay. Secondary end points included an analysis of the trends of open, laparoscopic, and robotic surgery in emergent colon and rectal surgery, and an analysis of how surgical procedures were decided upon.

Notably, 77.2% of CRC emergency surgeries were performed via an open approach at the start of the study period (2012), and no robotic surgeries were performed. By June 2021, open surgery accounted for 61.2% of these cases, with laparoscopy and robotic surgeries accounting for 32.2% and 6.6% of cases, respectively.

Ferrari D, Violante T, Novelli M, et al. Robotic surgery in emergency colorectal procedures: analysis of outcomes and future. 

Published July 23, 2025. doi:10.1097/XCS.0000000000001500

Articles

Outcomes favoring robotic surgery for CRC may be influenced by patient selection factors, including clinical stability.

Robotic Surgery Exhibits Benefit in Select Colorectal Cancer Procedures

In January 2025, the FDA approved sotorasib/panitumumab for patients with 

G12C-mutated CRC based on prior findings from the CodeBreaK 300 trial.

Sotorasib (Lumakras) plus panitumumab (Vectibix) improved patient-reported outcomes (PROs) at different doses vs investigator’s choice of trifluridine/tipiracil (Lonsurf) or regorafenib (Stivarga) among patients with 

G12C-mutated chemorefractory metastatic colorectal cancer (CRC), according to updated findings from the phase 3 CodeBreaK 300 study (NCT05198934) published in 

From baseline to week 9, the estimated least squares mean change in fatigue at its worst was –0.48 (95% CI, –1.18 to 0.23) with sotorasib at 960 mg plus panitumumab, –0.17 (95% CI, –0.86 to 0.52) with sotorasib at 240 mg plus panitumumab, and 0.42 (95% CI, –0.35 to 1.19) with investigator’s choice of therapy. In each respective arm, the estimated least squares mean change from baseline to week 9 was –0.83 (95% CI, –1.50 to –0.15), –0.52 (95% CI, –1.18 to 0.15), and 0.63 (95% CI, –0.11 to 1.36) for pain at its worst; 4.23 (95% CI, –1.39 to 9.85), 1.29 (95% CI, –4.13 to 6.70), and –5.21 (95% CI, –11.27 to 0.86) for global health status quality of life (GHS-QOL); and –0.27 (95% CI, –4.54 to 4.00), 0.69 (95% CI, –3.44 to 4.81), –5.66 (95% CI, –10.24 to –1.07) for physical function.

Overall, investigators noted a meaningful improvement in pain at its worst for both sotorasib doses, in GHS-QOL with sotorasib at 960 mg, and in physical function with sotorasib at 240 mg. In the sotorasib at 960 mg, sotorasib at 240 mg, and investigator’s choice arms, respectively, the median time to deterioration was 16.09 weeks (95% CI, 9.54-not estimable [NE]), NE (95% CI, 10.68-NE), and 8.97 weeks (95% CI, 5.84-18.37) for fatigue at its worst; 33.17 weeks (95% CI, 15.38-45.42), NE (95% CI, 12.39-NE), and 12.24 weeks (95% CI, 8.11-NE) for pain at its worst; and 19.93 weeks (95% CI, 8.40-34.17), 13.52 weeks (95% CI, 8.68-NE), and 12.39 weeks (95% CI, 8.26-NE) for GHS-QOL.

“[T]he combination of sotorasib [at] 960 mg and panitumumab not only significantly improved clinical outcomes but also resulted in better PROs that covered domains related to fatigue, pain, and disease-related and treatment-related symptoms and functions. Although not statistically tested, the combination also showed decreased risk of deterioration compared with investigator's choice of trifluridine/tipiracil or regorafenib,” lead study author Dominik Paul Modest, MD, a professor in the Department of Hematology, Oncology, and Cancer Immunology at Charité–Universitätsmedizin Berlin, wrote with coauthors in the publication.

 “In the context of the exploratory nature of the PRO analyses, these findings suggest that sotorasib [at] 960 mg combined with panitumumab could represent a valuable new treatment for patients with 

 G12C-mutated chemorefractory metastatic [CRC] with a favorable profile concerning its effects on [QOL].”

In the open-label CodeBreaK 300 trial, 160 patients were randomly assigned to receive sotorasib at 960 mg daily plus panitumumab at 6 mg/kg every 2 weeks (n = 53), sotorasib at 240 mg plus panitumumab at the same dose (n = 53), or investigator’s choice of trifluridine/tipiracil or regorafenib (n = 54). Treatment in the investigator’s choice arm consisted of trifluridine/tipiracil at 35 mg/m

 on days 1 to 5 and 8 to 12 twice a day orally or regorafenib at 160 mg orally each day for the first 21 days of each cycle.

The trial’s primary end point was progression-free survival, with secondary end points including overall survival and objective response rate. In these secondary and exploratory analyses, PRO questionnaires included the Brief Fatigue Inventory, Brief Pain Inventory, the GHS-QOL and physical function subscales of the European Organisation for Research and Treatment of Cancer QOL Questionnaire Core 30 (EORTC QLQ-C30), Patient Global Impression of Change (PGIC) Questionnaire, and GP5 single item of the Functional Assessment of Cancer Therapy—General questionnaire (FACT-G GP5).

G12C-mutant chemorefractory metastatic CRC who were naive to KRAS G12C inhibitor therapy, measurable disease per RECIST v1.1 guidelines, and an ECOG performance status of 0 to 2 were eligible for enrollment on the trial.

The median age was 63 years (range, 37-79) in the sotorasib at 960 mg arm, 58 years (range, 34-82) in the sotorasib at 240 mg arm, and 65 years (range, 34-81) in the investigator’s choice arm. Across the treatment arms, 44% to 55% were male, 57% to 79% were White, and 83% to 100% were not Hispanic. Additionally, 68% to 72% had liver metastases, 55% to 67% had an ECOG performance status of 0, and 53% to 69% had left-sided disease.

Modest DP, Fakih M, Salvatore L, et al. Health-related quality of life in patients with KRASG12C-mutated chemorefractory metastatic colorectal cancer treated with sotorasib plus panitumumab or standard of care (CodeBreaK 300): results from a phase 3, randomized clinical trial. 

Published online August 11, 2025. doi:10.1016/S1470-2045(25)00352-3

FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. News release. FDA. January 16, 2025. Accessed August 12, 2025. https://shorturl.at/1WviB

Data suggest that sotorasib plus panitumumab may represent a valuable new treatment option in this KRAS G12C-mutated colorectal cancer population.

Sotorasib Combo Improves Patient-Reported Outcomes in KRAS G12C+ CRC

At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, 

, an associate professor of medicine at the Medical College of Wisconsin, and 

, an oncologist/hematologist at Citizens Memorial Hospital, discussed the application of talquetamab-tgvs (Talvey) in relapsed/refractory multiple myeloma. The discussion, part of a 

, centered on updated results from the phase 1/2 MonumenTAL-1 trial (NCT03399799; NCT04634552) shared at the meeting.

Talquetamab has a unique place in the treatment paradigm for multiple myeloma as it is the only approved bispecific antibody targeting GPRC5D for relapsed/refractory multiple myeloma. Regarding this mechanism of action, Dhakal said, “The exact function and mechanism of this target is not understood; however, we know it is expressed heavily on the malignant plasma cells, much more than the normal plasma cells.”

With an extended median follow-up ranging from 30 to 38 months, the trial’s results continued to demonstrate consistent or improved efficacy and safety outcomes.

Patients in the trial were assigned to 1 of 3 treatment cohorts: the first (weekly dosing) enrolled patients who were naive to T-cell redirection therapy (TCR) and received 0.4 mg/kg of subcutaneous talquetamab once weekly (n = 143), the second (every 2-week dosing) enrolled patients who were TCR-naive who were administered 0.8 mg/kg of subcutaneous talquetamab once every 2 weeks (n = 154), and the third (prior TCR weekly and every 2-week dosing) enrolled patients who received prior TCR and were administered either 0.4 mg/kg once weekly or 0.8 mg/kg once every 2 weeks (n = 78).

In the first cohort, the overall response rate (ORR) was 74.1%, with a complete response (CR) or better rate of 32.9%, a very good partial response (VGPR) rate of 26.6%, and a PR rate of 14.7%. In the second cohort, the ORR was 69.5%, with a CR or better rate of 40.3%, a VGPR rate of 18.8%, and a PR rate of 10.4%. In the third cohort, the ORR was 66.7%, with a CR or better rate of 42.3%, a VGPR rate of 12.8%, and a PR rate of 11.5%.

Notably, however, in the first and second cohorts, the patients were naive to TCR, whereas in the third cohort, they received prior TCR. Shunyakov said, “It’s pretty incredible to see that the response rate in patients who had prior exposure to T-cell–redirected therapy is about the same as in patients who are naive to TCR.”

Further, the median duration of response (DOR) was 9.5 months (95% CI, 6.7-13.4) in the first cohort, 17.5 months (95% CI, 12.5-25.1) in the second cohort, and 19.2 months (95% CI, 8.1-24.7) in the third cohort.

“If you look at the durability of response, that is where the significance of this product comes in,” said Dhakal. “If you look at the 0.8 mg/kg [subcutaneous] every other week, your median DOR is almost 18 months. That is quite impressive.”

He emphasized the similarity in DORs between the second cohort, which did not receive prior TCR, and the third cohort, which did. Shunyakov agreed that the positivity of these results, especially in the prior TCR cohort, was impressive. With these high and durable responses in this group of patients with an unmet need for new therapies, it is crucial to consider talquetamab for treatment, according to Dhakal.

Dhakal also pointed out that data from the benchmark studies from when CAR T-cell therapies were initially developed—the MAMMOTH and LocoMMotion (NCT04035226) studies—showed an overall survival (OS) of less than a year.

MonumenTAL-1 data significantly improved on that by showing prolonged survival in the same unexposed patient population and also in patients with prior exposure to T-cell–directed therapies.

The findings showed a median OS of 34.0 months (95% CI, 25.6-not estimable [NE]) in the first cohort, not reached (95% CI, NE-NE) in the second cohort, and 28.3 months (95% CI, 19.5-NE) in the third cohort. The respective 36-month OS rates were 49.3% (95% CI, 40.4%-57.6%), 60.8% (95% CI, 51.5%-68.8%), and 44.6% (95% CI, 31.4%-57.0%).

“In terms of overall survival, [these] data [are] unprecedented,” Shunyakov added.

In cohorts 1, 2, and 3, respectively, the median progression-free survival (PFS) was 7.5 months (95% CI, 5.7-9.4), 11.2 months (95% CI, 7.7-14.6), and 7.7 months (95% CI, 4.1-14.5).

Both clinicians also discussed the heavily pretreated patient population of the trial, as having 3 or more therapies was a requirement to enroll in phase 2; in the TCR-naive population, the median number of lines of therapy was 5, and in the TCR-exposed population, it was 6. Considering the positive data, even in this population, Shunyakov said it would be good to consider moving talquetamab up and treating patients with it as soon as possible. Dhakal highlighted that, as with most highly effective therapies, if you move them earlier, they will elicit better responses.

He also noted that, as patients require more lines of therapy, they are more likely to drop out of treatment, so waiting to administer it may be inadvertently preventing many patients from having the opportunity to receive this therapy.

With the trial broken down into 3 cohorts, several trends were noticeable. The first Shunyakov mentioned was how the weekly dosing schedule in the first cohort elicited higher responses, whereas the biweekly dosing schedule from cohort 2 demonstrated prolonged OS and PFS.

This likely means that biweekly dosing was better tolerated, and thus, patients can stay on treatment longer and continue to derive benefit. In his practice, Shunyakov has been administering talquetamab in the biweekly dosing schedule, almost from the beginning.

They do this because talquetamab can lead to mucositis, skin problems, and weight loss, which can become serious issues if they overadminister the drug.

Dhakal also uses the 0.8-mg/kg biweekly dosing schedule because it is convenient for the patient, and if the patient maintains their response, they may change to monthly dosing. According to him, no observable difference exists between the weekly and biweekly schedules regarding controlling the disease.

“There are no clinical predictors that will help you choose one dose vs another, but 0.8 mg/kg seems to be more friendly for the patient,” said Dhakal.

Shunyakov also stated that, in patients with prior exposure to BCMA, his next choice for therapy would be to target GPRC5D.

At the extended follow-up, the safety profile remained consistent with what was previously seen. Discontinuation rates due to adverse events (AEs) remained low, and no new discontinuations were observed due to GPRC5D-related AEs. However, a new safety signal, ataxia/balance disorders, was identified in association with talquetamab and had a low prevalence in MonumenTAL-1. The most common AEs of grades 3 and 4 were cytopenias, and there were no reported treatment-related deaths due to talquetamab.

Both doctors emphasized the infection-related AEs. Any-grade and grade 3/4 infections occurred in 61% and 23% of cohort 1, 71% and 21% of cohort 2, and 78% and 26% of cohort 3, respectively.

Although these rates are significant, Shunyakov compared them with the infection rates of BCMA-directed bispecific antibodies, which are close to 70% for any grade and 50% for grades 3/4. As he said, talquetamab is favorable. He attributed this to the mechanism of action of talquetamab because it primarily targets multiple myeloma cells rather than other plasma cells, which have very minimal or no effect on the healthy B lymphocytes. He added that he may even prefer talquetamab before a BCMA-
directed bispecific antibody due to the lower rate of infections.

For prophylaxis, although patients who receive BCMA-
directed bispecific antibodies almost always receive intravenous immunoglobulin replacement therapy, when patients who received talquetamab are several months into treatment, their immunoglobulin levels increase in most cases. In other words, most patients receiving talquetamab receive prophylaxis early on in treatment but may discontinue it later.

The new safety signal, ataxia/balance disorders, was also a point of conversation. Although neither doctor has seen it in practice yet, they have made it a point to tell their patients that it is a potential new toxicity that can be debilitating, even if it only occurs in less than 1% of patients.

Rasche L, Schinke CD, Touzeau C, et al. Efficacy and safety from the phase 1/2 MonumenTAL-1 study of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma: analyses at an extended median follow-up. 

. 2025;43(suppl 16):7528. doi:10.1200/JCO.2025.43.16_suppl.7528

Experts discussed talquetamab's unique mechanism and favorable patient outcomes in relapsed/refractory multiple myeloma. 

Analyzing Long-Term Follow-Up Results From MonumenTAL-1 in Multiple Myeloma

Collaboration Brings “Excitement” to Novel Cancer Therapy Development

Coyne 5

The opportunity to explore novel therapeutic agents and bring more complex immunotherapies to the community setting represents an “exciting aspect” of the collaboration between Northwell Health and the Southern Texas Accelerated Research Therapeutics (START) Center for Cancer Research, said Geraldine O’Sullivan Coyne, MD, MRCPI, PhD.

In July 2025, Coyne was appointed as the principal investigator and director of Clinical Research at the Northwell Health unit of the START Center for Cancer Research, which will be based in R.J. Zuckerberg Cancer Center in New Hyde Park. Coyne spoke with CancerNetwork

 regarding the next steps and initiatives for further expanding access to treatment and early phase clinical trials among patients with cancer living in community settings.

According to Coyne, an exciting aspect of drug development in oncology is seeing the delicate engineering of molecules to make novel agents like antibody drug conjugates more manageable in terms of safety and toxicity management. She noted that the partnership between Northwell Health and START may continue to advance this pursuit of developing new drugs in oncology while creating more targeted approaches for patients.

It’s always hard to think ahead. The most exciting aspect of drug development in oncology has been the delicate engineering of novel molecules that have been increasingly potent and either [significantly] less toxic or with a toxicity pattern that we have been able to manage, prevent, and/or mitigate. It has been [quite] exciting to see these newer molecules, such as antibody drug conjugates, starting to become part of mainstream therapy for patients with advanced malignancies.

[Much] of the excitement surrounding the START unit and Northwell Health collaboration with them is exploring these novel molecules that will hopefully continue to build on the pursuit in oncology drug development, which has been finding better and more targeted therapies for patients in their treatment journey. The most exciting aspect of working in this area, and indeed being able to partner with Northwell Health, is to explore these novel drugs and take on these newer and exciting complex immunotherapies in the community.

Olt B. Northwell names Geraldine O’Sullivan Coyne, MD, PhD, to lead clinical trials at new START center. News release. Northwell Health. July 22, 2025. Accessed August 7, 2025. https://tinyurl.com/bdcua8ck

Videos

Geraldine O’Sullivan Coyne, MD, MRCPI, PhD, described the excitement of seeing novel molecules like antibody drug conjugates become more prominent.

Results from a retrospective study showed that chemoimmunotherapy did not prolong survival vs chemotherapy in a younger ES-SCLC population.

Chemoimmunotherapy may not confer a survival benefit and result in more immune-related adverse events (AEs) and hematologic toxicity compared with chemotherapy in younger patients with extensive-stage small cell lung cancer (ES-SCLC), according to results from a multicenter, retrospective study shared in 

Overall, with a median follow-up of 13.7 months, the median progression-free survival (PFS) was 4.67 months in the younger group and 5.40 months in the control group (

<.001); the median overall survival (OS) was 13.70 months vs 14.37 months, respectively (

In the group of patients who received chemoimmunotherapy, the median PFS was 4.50 months in the younger group vs 5.57 months in the control group (

= .002); the median OS was 13.20 months vs 15.33 months (

= .012). The overall response rate (ORR) was 68.97% in the younger group vs 78.70% in the control group (

 = .271), showing a nonsignificant difference. The disease control rate (DCR) was 96.55% in the young group, with 0 complete responses (CRs), 20 partial responses (PRs), 8 instances of stable disease, and 1 instance of progressive disease.

In the patients who received chemotherapy, the median PFS was 4.75 months vs 5.37 months in the younger group and control group, respectively, showing no significant difference (

= .082); the median OS was 13.70 months vs 13.73 months, also showing no significant difference (

= .407). The ORR was 60.0% in the younger group vs 80.0% in the control group (

= .016). The DCR was 96.67% in the younger group, with 0 CRs, 18 PRs, 11 instances of stable disease, and 1 instance of progressive disease.

No statistically significant difference was observed regarding ORR and DCR between the young chemoimmunotherapy and chemotherapy groups. Kaplan-Meier survival analyses revealed no significant differences in PFS or OS between the young chemoimmunotherapy and chemotherapy groups either: 4.50 months vs 4.75 months for PFS (

= .501), and 13.20 months vs 13.70 months for OS (

In a univariate analysis considering all patients who received chemoimmunotherapy, the factors negatively associated with PFS were younger age (HR, 0.511; 95% CI, 0.333-0.784; 

= .002) and liver metastases (HR, 1.629; 95% CI, 1.132-2.343; 

= .009); for OS, age stratification (HR, 0.556; 95% CI, 0.349-0.885; 

= .013), liver metastases (HR, 1.932; 95% CI, 1.281-2.915; 

= .002), and radiotherapy (HR, 0.440; 95% CI, 0.291-0.665; 

<.001) were significantly associated factors.

Separate Cox proportional hazards regression analyses, in the young group, demonstrated that radiotherapy was the only factor that significantly correlated with PFS and OS; univariate analyses revealed that radiotherapy improved PFS (HR, 0.496; 95% CI, 0.286–0.859; 

= .012) and OS (HR, 0.207; 95% CI, 0.104–0.411; 

“Young patients with ES-SCLC exhibited poorer survival outcomes, with shorter PFS and OS compared to the control group,” wrote lead study author Lijuan Zhao, of the Senior Department of Oncology at The Fifth Medical Center of PLA General Hospital in Beijing, China, and the Graduate School of Chinese PLA General Hospital, with coauthors in the publication. “Chemoimmunotherapy may not demonstrate a survival advantage in young patients, as evidenced by similar PFS and OS outcomes compared to chemotherapy.”

The retrospective analysis included 347 patients with ES-SCLC, of whom 210 received chemotherapy and 137 received chemoimmunotherapy. Patients were further broken into a young group (n = 59), consisting of patients 45 years or younger, and a control group (n = 288), consisting of patients older than 45 and 75 years or younger. Chemotherapy consisted of etoposide and platinum-based drugs; when indicated, immune checkpoint inhibitors (ICIs) were added to therapy.

Eligible patients were 18 years to 75 years old with pathologically or cytologically confirmed ES-SCLC without prior systemic treatment, an ECOG performance status of 0 or 1, and at least 1 measurable lesion per RECIST v1.1 guidelines. Among the reasons for exclusion were limited-stage SCLC, previous platinum-free chemotherapy, and combined disease with non–SCLC.

Trial end points were PFS, OS, safety, and responses among the different age groups.

In the younger group, the median patient age was 40 years (IQR, 37.0-42.0) in the chemoimmunotherapy group and 39.5 years (IQR, 36.3-42.0) in the chemotherapy group; in the control group, it was 62 years (IQR, 57.0-68.0) and 62 years (IQR, 56.0-67.3). The majority of patients in all groups were male, had an ECOG performance status of 0, and had prior smoking history.

Immunotherapy was anti–PD-1 drugs in 51.7% of the younger group and 33.3% of the older group, and anti–PD-L1 drugs in 48.3% and 66.7%. The most common chemotherapy regimen was etoposide plus carboplatin, except for in the younger chemotherapy group, where it was etoposide plus cisplatin.

Regarding safety, 86.44% of the younger group and 82.97% of the control group experienced a treatment-related AE (TRAE). The most common AEs were hematologic toxicity and gastrointestinal toxicity; the younger group had a higher incidence of thrombocytopenia (25.42% vs 14.24%; 

= .033). Immune-related AEs occurred in 30.51% of the younger group and 11.46% of the control group (

<.001); they included pneumonitis (11.86% vs 2.43%; 

“These findings suggest that chemoimmunotherapy may not be as effective in young patients with ES-SCLC and underline the need for tailored treatment strategies in this population,” the study authors concluded.

Zhao L, Xiong Q, Long Y, et al. Efficacy and safety of first-line chemoimmunotherapy in young patients with extensive-stage small cell lung cancer: a multicenter retrospective study. 

. 2025;25(1):1136. doi:10.1186/s12885-025-14524-y

Results from a retrospective study showed that chemoimmunotherapy did not prolong survival vs chemotherapy in a younger ES-SCLC population. 

Chemoimmunotherapy Less Safe, Efficacious in Younger ES-SCLC Population

On a spring evening in Philadelphia, Pennsylvania, experts in multiple myeloma gathered to debate treatment options in the relapsed/refractory setting. The teams competed in 3 key areas: real-world updates, B-cell maturation antigen (BCMA) or chimeric antigen receptor (CAR) T-cell therapy sequencing, and patient cases.

 An educational program designed as a competition for teams to present to and against each other.

 There are 3 rounds: data presentations, topics, and patient cases. During each round, both teams can present and defend their ideas and challenge the other team. The judge determines who is worthy of the top prize.

Team Eagles on Real-World Ide-Cel Results

This real-world data set from the Center for International Blood and Marrow Transplant Research (CIBMTR) assessed patients with relapsed/refractory multiple myeloma.

 The data set compared the CIBMTR registry (n = 603) with results from the phase 2 KarMMa trial (NCT03361748; n = 128).

Between the registry and the trial, the patient characteristics included a median age of 65 years vs 61 years, with 26% vs not available for 70 years or older; 36% vs 26% had penta-refractory disease, and 5% vs 0% had received prior BCMA CAR T-cell therapy. Additionally, 17% vs 39% of patients in the CIBMTR registry and the KarMMa trial had extramedullary disease, 23% vs 35% had high-risk cytogenetics, 16% vs 16% had International Staging System stage III, and the median lines of prior therapy were 7 and 6, respectively.

Efficacy outcomes included a 6-month progression-free survival (PFS) rate of 62% in the CIBMTR registry and a 6-month overall survival (OS) rate of 82%. In the KarMMa trial, the median PFS was 8.6 months, and the median OS was 24.8 months. The overall response rate (ORR) was 71% vs 73%, the very good partial response rate was 53% vs 52%, and the complete response rate or better was 27% vs 33%, respectively.

Notably, cytokine release syndrome (CRS) occurred in 81% of patients in the CIBMTR registry and 84% in the KarMMa trial, with 3% and 5% having grade 3 or higher. Additionally, neurotoxicity was noted in 27% vs 18%, with 4% vs 3% having grade 3 or higher.

A study by Ferreri et al assessed prior BCMA-targeted therapy and idecabtagene vicleucel (ide-cel; Abecma) use.

 For those with prior BCMA therapy, the ORR was 74%, and for those without it, the rate was 88%. Based on the type of prior BCMA therapy, the ORR for those given antibody-drug conjugates (ADCs) was 68%, 86% for those who received bispecifics, and 100% for those who were given CAR T-cell therapy.

Thirty-eight patients received an ADC, mainly belantamab mafodotin-blmf (Blenrep), and 7 patients had not received a prior bispecific antibody.

For those with prior BCMA therapy, the PFS was 3.2 months vs 9.0 months (

 = .0002) for those without, and the OS was not reached vs 12.5 months (

 = .005). For those given an ADC, the PFS was 3.2 months; those given bispecifics had a PFS of 2.8 months, and prior CAR T-cell therapy had a PFS that was not reached (

 / I was fascinated by the graph of the different types of prior therapies, because I would have expected the opposite––that patients who had [received] prior ADC with belantamab would probably have a good response to CAR T cells, whereas patients who had [received] a prior bispecific aimed at BCMA would be more likely to have a BCMA-negative relapse and therefore less response to CAR T cells.

 / Looking at it initially, it is a little surprising, I agree. The details that aren’t here are how soon after these drug exposures, and did they get their CAR T products? Did it just so happen that they got belantamab right before CAR T, and that maybe would influence response rates? For some reason, there was a longer duration between bispecifics and CAR T therapy because we know the longer you’re off with BCMA-targeted therapy, that’s the predictor of response to CAR T. There wasn’t as much detail here to explain this.

 / It’s not surprising [about] the 68% [ORR] in the ADC cohort, but it was striking that this very small number of a total of 12 patients who got T-cell redirecting therapy did incredibly well. They were probably just lucky patients, and 2 received ide-cel, relapsed, received ide-cel again, and responded again. So that’s interesting.

 / If there’s any real takeaway from this real-world study, it’s that those PFS numbers are disappointing. The PFS in the registrational pivotal study was something like close to a year, but in this case, we’re not even seeing more than 9 months. I remember seeing the original ide-cel data from the KarMMa-1 trial, and thinking, “I don’t know if it would beat salvage [therapy]”. It’s just interesting that with BCMA CARs, there’s just such a wide range of responses. It’s different than the CD19 CARs, where there are all these different CD19 CARs out there with different designs and costimulatory domains, and they all work the same. In BCMA, you have some BCMA CARs that went into the clinic and had no responses. There was one…we brought in that had…so-so responses. Then you have ide-cel, which is in the middle, and then you have ciltacabtagene autoleucel [cilta-cel; Carvykti], which is extraordinary. No one has figured out why one works and the other doesn’t.

Patients with relapsed/refractory multiple myeloma who had received 2 to 4 prior regimens and were treated with either ide-cel or 1 of 5 standard therapies were enrolled in the phase 3 KarMMa-3 trial (NCT03651128).

 Select baseline characteristics included prior treatments, which included either an immunomodulatory agent (88% vs 94%), a proteasome inhibitor (74% vs 72%), or an anti-CD38 monoclonal antibody (95% vs 94%). The median time from diagnosis to screening was 4.1 years in the ide-cel group and 4.0 years in the standard of care group. Additionally, 65% vs 67% of patients had triple-class refractory disease, and 95% vs 93% had disease refractory to daratumumab.

The final PFS analysis highlighted an 18-month PFS rate of 41% in the ide-cel arm vs 19% in the standard-of-care arm. The median PFS was 13.8 months and 4.4 months (HR, 0.49; 95% CI, 0.38-0.63).

In the ide-cel arm, hematologic adverse effects (AEs) of any grade occurred in 90% of patients, grade 3/4 in 93%, and grade 5 in 14%. Any-grade nonhematologic AEs occurred in 58%, grade 3/4 in 24%, and grade 5 in 4%. In the standard regimen arm, any-grade hematologic AEs occurred in 98% of participants, grade 3/4 in 75%, and grade 5 in 6%. Any-grade nonhematologic AEs occurred in 54%, grade 3/4 in 18%, and grade 5 in 2%.

 / What’s interesting to me about KarMMa-3 is that you see a similar pattern with the phase 3 CARTITUDE-4 [NCT04181827] trial. If you look at the responses and duration of response with ide-cel in the third line of therapy and compare it with ide-cel in the sixth line of therapy in KarMMa-1, it looks the same. It doesn’t look like the CAR T cells are working dramatically better when you use them in an earlier line of therapy, which is surprising. All of us anticipated that maybe we would see some cures and plateaus if we use them earlier with healthier T cells, and maybe the cilta-cel to look a little bit better, just like antimyeloma therapy would look a little bit better in the early line of therapy. We’re not seeing that they’re working better when you use them in an earlier line of therapy.

 / Keeping that in mind and looking at these curves and thinking about how the landscape of multiple myeloma has changed…, at what point are you thinking about CAR T vs bispecifics and then thinking about some of the newer bispecific data as well, and those PFS curves,…toxicity, and ease of access?

 / This trial also permitted crossover, which we hardly ever see in these types of trials. If you were on the control arm of the study, and you progressed, you could cross over to CAR T cells. Many patients in the control arm received CAR T cells in the next line of therapy. There was no difference in OS, which also informs our thinking about whether we should be rushing to give CAR T cells in the second line of therapy rather than the third or fourth line of therapy. It seems likely that your long-term survival is similar. It just gives you some reassurance that you don’t have to rush to give patients CAR T cells the minute they’re within the label. You can get them a next line of therapy and probably get the same long-term survival as when you’re talking about the risk of CAR T-cell therapy.

 / You could do the opposite argument, right? Maybe it’s too late because the way we enrolled these patients on the clinical trial, they have to have progressive disease. The disease is growing already on the second to third line. You’re not doing these freezes when the T cells might be the healthiest because they have this growing burden of multiple myeloma that can cause immune dysfunction. There are a lot of benefits in more correlational studies. [The data from] these studies will [enable] us to interpret it and try to choose, right? What’s the fingerprint of the patient who can wait vs the patient who needs this treatment right away?

 / It’s a good point. We need to keep in mind that we need 1 more potential salvage, even for bridging, which we all like to look at these days. Also, bringing [us] back to the real-world analysis, you may think they would…do better because these patients didn’t have to wait for confirmed progression [and] didn’t have limitations in bridging therapy, but they did pretty much the same. We still don’t know which subgroup of patients benefits most from each strategy.

Presented by Asya Nina Varshavsky-Yanovsky, MD, PhD​

 / When I may want to do bispecific before CAR T is when a patient is presenting to me as [having] refractory [disease], not second line and not third line. They are coming with an exploding disease. I would love to do CAR T. It will take me 3 weeks to get the patient to gluconeogenesis, and it will take me another 5 weeks to get the patient the actual CAR T product delivered to me. In the meantime, I’m OK with giving selinexor [Xpovio]. In this situation, I am extremely happy that I have those wonderful off-the-shelf products. We are talking about BCMA bispecific. I have 2 wonderful off-the-shelf products [where] I can admit the patients on the same day, see them with their exploding [disease], and start the ramp-up [doses]. The time to first response to these drugs is 1 cycle. The time to best response is around 3 cycles. The toxicity––unlike CAR T, where we are worried about increased toxicities, increased CRS, increased immune effector cell–associated neurotoxicity syndrome, terrible cytopenia, and so on, in patients who have extremely high disease burden––[for the] bispecific does apply, but on a much lesser scale. The toxicities are much more manageable. I can take this patient and this expectation of overall response upwards of 60%. I can get them in a [good], but also deep response. At the end of it, I may keep them on this wonderful drug for as long as they’re responding, which [could] potentially be years. Or I can design a stop date and see [what happens]. This will still not take away my opportunity to do CAR Ts [in the] next line of therapy.

 / Would you ever use a non-BCMA bispecific before doing a CAR T-cell therapy?

 / We are all worried about this type of sequencing with potential antigen loss, especially if we are continuing the bispecific through progression as opposed to doing preplanned debulking therapy and moving on to something else. We will not have this concern if we are using a GPRC5D bispecific. In terms of my choice of drug, there are many factors that will affect my choice of BCMA bispecific as opposed to GPRC5D bispecific. If I’m still dead set and getting this patient to BCMA CAR T sooner rather than later, I will offer a GPRC5D bispecific, like talquetamab-tgvs [Talvey]. We’ll plan CAR Ts [in the] next step. It will not take away all my concerns. It will take away my concerns about antigen loss. It will not necessarily take away my concern about T-cell fitness, T-cell exhaustion, or my ability to successfully collect and manufacture the CAR T product. If my goal is to get this very sick patient to CAR T with the hope of giving them this 3-plus years’ PFS from the CAR T, I will favor talquetamab. I will favor debulking and then some treatment holds and some treatment-free period in the hope of getting the T cells to their most functional state, followed by CAR T collection. I may just say, “OK, that’s a great line of therapy. Let’s ride it for as long as it works.” When we get there, we will plan CAR T all over again.

Team Phillies on CAR T Before Bispecifics

Presented by Sandra P. Susanibar-Adaniya, MD​

 / When I treat patients with multiple myeloma, I want to help them live the longest, but with the best quality of life. The [average] patient with multiple myeloma is already in their late 60s, early 70s when they’re diagnosed. What I want for them is the treatment that has a high chance of being effective and can maintain a good quality of life for the longest time. We know that CAR T cell works in [older] patients over the age of 80 with renal failure and has proved to be equally efficacious. If you have a patient who is going to get 1 treatment, and then it’s done, and is 70 and can live the best life ahead of [them] for the next 3 or 4 years and then get a bispecific plus a very good response, why wouldn’t I choose to do that? The risk of infections in CAR T cells is limited, so it’s mostly in the first 3 months, but then it goes down. We have become very good at trying to identify which measures can decrease the infection. It’s that critical period of 3 months that they need more care from us, but then they can go to the community [to receive treatment], and when they go back to the clinic and tell you about their best life, they go on vacation, they’re enjoying the retirement, so they are doing well.

The second thing for me is that you don’t know what’s going to happen later. These 3 years that they haven’t received therapy,…the landscape of multiple myeloma has changed so much in 3 years. You don’t know if they will benefit a lot from this limited- duration bispecific antibody. They get 3 years of treatment, then they get 6 months of bispecific, and then they get maybe…2 more years of treatment. They have this ability to live well.

Then the other thing is the percentage of patients that need treatment because they cannot get to CAR T cells, now that we have the option to do it at second or third line, because it’s approved, it’s reduced. It’s less than 10% [of patients for whom] they did these extraordinary measures that we can do. Maybe we can do just a limited-time bispecific, but for most patients, the treatment that I would prefer is to do CAR T cells and then bispecific, if there are no other CAR T cells that will be approved for patients who have already progressed to CAR T cells.

 / For exactly the reasons you said, bispecific before CAR T is perfect. Our goal is to get them to CAR T and maximize their quality of life and durability response. Using a bispecific, like a GPRC5D bispecific, as a holding or bridging phase in which you’re doing it, is an ideal place to use a drug like talquetamab and then get them to CAR T afterward. Because you decrease their disease burden, you minimize that GPRC5D toxicity by just giving a couple of doses. Then you bring them to CAR T afterward. You do bispecific before CAR T. Then, by decreasing their disease burden, you’re minimizing the toxicity that you may experience with CAR T if you try to bring them straight to CAR T without anything beforehand. You may even augment some T-cell activity by doing a bispecific with a different target before a BCMA-targeted CAR T, and then maybe even get a better PFS than you otherwise would have seen with better tolerability and overall better quality of life.

 / What you’re saying is applicable only to patients with incredibly high-risk or high-proliferative disease, where you’re going to be turning to a super-toxic drug like talquetamab for bridging therapy or before going to CAR T cells. For the vast majority of patients, you want to use a treatment that’s going to have the longest PFS, the best data on OS, first, especially because if you go to a CAR T cell first, your likelihood [is] that way down the line, the disease is going to relapse still with the same antigens intact and therefore have better responses to both BCMA, bispecific, GPRC5D, or FCRH5 bispecific whenever it finally gets approved. Those antigens, especially BCMA, are still likely to be there and have to relapse from CAR T, whereas if you go first to a BCMA bispecific, for instance, then you’re possibly leaving yourself without a great option afterwards. It’s only in the highest-risk patients, the patients where you don’t have the option, that you’re going to go to a bispecific first, whether it’s going to a BCMA bispecific because the patient needs something right this second, or using something like talquetamab as a bridging [therapy]. [For] most…patients, you’re going to want to do CAR T cells first.

• A 70-year-old fit patient with standard-risk, triple-class–exposed relapsed/refractory multiple myeloma, naive to BCMA-targeted therapies, presents for treatment options.

• After progressing on proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, the patient is eligible for cilta-cel therapy.

• This therapy has shown an ORR of 97% and a median PFS of 34.9 months in BCMA-naive populations.​

 / I want to know the detailed pathophysiology of the mechanisms and the underlying difference.

 / We had a very detailed and heated discussion of whether we want to expose patients when they are planning for BCMA and CAR T to BCMA bispecific, or if we even want to ever do BCMA and CAR T as opposed to BCMA bispecific. That points to prior BCMA exposure decreasing efficacy, including response rates and response duration to BCMA CAR T, and we should also keep in mind that this patient is 70 years old and fit, and potentially maybe less fit and older, if we delay CAR T to the next line of therapy at that time. There is a very strong argument for proceeding with cilta-cel in a patient who is 70 years old and fit, who right now seems to be a good candidate who can handle toxicity and can enjoy the 3 years of PFS as opposed to delaying it.

 / Do we have enough data about the current practice of prior BCMA-targeted exposure?

 / I agree. The data on CAR T cells after prior BCMA-directed therapy are limited. Some of those papers we saw before were talking about [roughly] 7 patients who [received] a prior bispecific and then CAR T cells. The reason is that the more typical patient who [had] a bispecific first, say, on a clinical trial, is still in response. We still have a lot to learn about a typical patient who gets a prior BCMA bispecific, has a good response for a long time, and then progresses [to] what their outcomes are after CAR T-cell therapy. We’ll learn with time. The reason why we feel a lot more comfortable with the opposite sequence is more…that there’s been a much larger volume of reported experience of CAR T cells, and then bispecifics, just the nature of the timing of when these different trials were done. There was just a much larger experience with it so far.

• A 62-year-old patient with standard-risk, triple-class–exposed relapsed/refractory multiple myeloma presents after 3 prior lines of therapy failed, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies.

• The patient is fit and eligible for ide-cel therapy, demonstrating improved PFS (13.8 months vs 4.4 months with standard regimens) and a higher ORR (71% vs 42%) in this population​.

 / [Regarding] bridging therapy, this is something…we’ve [become] much better at than [what] we used to do on our clinical trials. I don’t even know what the rules were in the ide-cel trials, but in the cilta-cel trials, a lot of times, they had tremendous restrictions on bridging therapy. I guess we’re there to try to make it so that the CAR T cells would not appear better than they were by people getting amazing bridging therapy. We’re seeing that by using good bridging therapy, we can make it easier for people to get through the CAR T cells. We were having a theoretical discussion earlier about whether there is such a thing as too good bridging therapy, where there’s not enough antigen left for the CAR T cells. Maybe we’ll find that out someday, but so far, I don’t think we’ve seen that. Even more than that, in my clinical practice now, [I] treat patients first with something for relapsed/refractory multiple myeloma. Then, as they’re responding to therapy, that’s when I do my apheresis, and then continue the same regimen for bridging. It’s bringing the bridging therapy even before apheresis. That feels like it’s been an effective technique for making the whole process more manageable.

 / In some ways, the big value of having these available earlier has just improved the safety and feasibility. It’s no longer this ranked thing where you’re between scheduling the manufacturing and dealing with relapsed/refractory disease. It just feels very manageable now when you have a good bridging option open. Now that we have readily available manufacturing slots, it’s just a lot easier.

 / We’ve forgotten, a couple of years ago, that we were so limited in the number of cilta-cel slots we had, and basically, we took whatever slot we could get; that was the choice of the product in some ways. Now that has been eliminated as a major barrier. I would say the only somewhat common barrier, and it’s less than 20%, but I would say there are some more manufacturing failures, or at least under specification, for cilta-cel that I’ve seen than ide-cel. Therefore, that…raises the question, if that occurs, do you keep trying to harvest more cells or do another manufacturing, or is that a reason to switch to ide-cel more quickly to get a patient moving along with a BCMA- directed CAR T-cell therapy? But in some ways, that has been my personal practice. The older patients, where I am concerned about the potential toxicity, and then the patients who have some manufacturing difficulty with cilta-cel, are my most common ide-cel uses.

 / The turnaround time for ide-cel is also a little faster than cilta-cel, which is nice. The cilta-cel specifications are very persnickety.

Sidana S, Ahmed N, Akhtar OS, et al. Real world outcomes with idecabtagene vicleucel (ide-cel) CAR-T cell therapy for relapsed/refractory multiple myeloma. 

. 2023;142(suppl 1):1027. doi:10.1182/blood-2023-181762

Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. 

. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850

Ferreri CJ, Hildebrandt MAT, Hashmi H, et al. Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy. 

. 2023;13(1):117. doi:10.1038/s41408-023-00886-8

Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. 

. 2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614

Experts debate cutting-edge multiple myeloma treatments, exploring pressing data, the most prominent news, and patient cases.