Strategic Timing for CAR T in R/R MM: The Importance of Early Referral

Video content above is prompted by the following:

When should physicians start thinking about referring their patients to CAR T? Why is early referral or allowing access to CAR T in earlier lines of therapy critical for patients with R/R MM?

Please comment on any similarities and/or differences regarding the ideal or most appropriate timing for CAR T referral, especially for those patients treated in the community.

Videos

Experts discuss when physicians should consider referring patients to chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory multiple myeloma (R/R MM). They emphasize the importance of early referral and access to CAR T in earlier lines of therapy while commenting on the similarities and differences in referral timing, particularly for patients treated in the community.

Cilta-cel vs. Ide-cel: Key Data Updates and Clinical Decision-Making in R/R MM

How are you deciding between utilizing cilta-cel vs ide-cel, and what factors (disease, patient, and/or product) impact that decision?

KarMMA-3 with ide-cel also recently reported its final PFS analysis

What were some highlights of this data, and what areyour impressions so far?

There was a recent update from ASH 2024 regarding the MRD negativity rates from CARTITUDE-4 with cilta-cel; what were some of your key takeaways, and have the data impacted your clinical practice?

Experts discuss how they decide between utilizing cilta-cel vs ide-cel in multiple myeloma, considering factors like disease characteristics, patient factors, and product differences, while reviewing the final progression-free survival (PFS) analysis from the KarMMA-3 study with ide-cel and key takeaways from the ASH 2024 update on minimal residual disease (MRD) negativity rates from CARTITUDE-4 with cilta-cel and its impact on clinical practice.

Sequencing CAR T in More Heavily Pretreated R/R MM as well in patients who deferred initial autologous HSCT

What is your clinical approach to CAR T-cell therapy in R/R MM? How are you typically sequencing CAR T with the other available treatment options like autologous HSCT and bispecifics?

Experts discuss their clinical approach to using chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory multiple myeloma (R/R MM), focusing on how they sequence CAR T with other treatment options like autologous hematopoietic stem cell transplantation (HSCT) and bispecific antibodies.

Optimizing CAR T in R/R MM: Treatment Paradigms and Patient Selection

Where does CAR T-cell therapy currently fall in your treatment paradigm? What type of patient factors and/or disease characteristics influence your approach?

Experts discuss where chimeric antigen receptor (CAR) T-cell therapy currently fits in the treatment paradigm, highlighting the patient factors and disease characteristics that influence its use in clinical decision-making.

Surbhi Sidana, MD, assistant professor, medicine, Department of Medicine, Division of Blood and Marrow Transplantation & Cellular Therapy, leader, Myeloma Cellular Immunotherapy program, Stanford University School of Medicine, discusses the unmet needs for patients with relapsed/refractory multiple myeloma who could be candidates for CAR T-cell therapy but have impaired renal function, and how clinical trials for these therapies have excluded this subset of patients.

BCMA-directed CAR T-cell therapies represent a promising treatment option for patients with relapsed/refractory multiple myeloma, and the FDA has approved 2 products for patients who have received at least 4 lines of prior therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody: idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel, Carvykti), Sidana begins. 

 based on results from the phase 2 KarMMa trial (NCT03361748), and 

 based on findings from the phase 1b/2 CARTITUDE-1 trial (NCT03548207). 

However, in both trials, investigators excluded any patients with renal impairment, Sidana explains. Renal impairment affects a significant proportion of patients with multiple myeloma, including up to one-fourth of patients at diagnosis and an even higher proportion of patients at the time of relapse, Sidana notes.

In a retrospective analysis presented at the 2023 Transplantation & Cellular Therapy Meetings

, investigators looked at real-world outcomes for patients treated with ide-cel. Findings showed that regarding safety, the rates and severity of cytokine release syndrome and neurotoxicity were similar between the patients with renal impairment and those with normal renal function. Additionally, the overall response rates and median progression-free survival were comparable between the 2 groups.

Because clinical trials are often highly selective when enrolling patients, patients with reduced renal function are sometimes left out, Sidana adds. In the studies of ide-cel and cilta-cel, this may have stemmed from a lack of a full toxicity and safety profile for the CAR T-cell therapies, which are still new to the myeloma space, Sidana says. Given the findings of the real-world retrospective study, once it established that there is a product that works, investigators should be inclusive of other cohorts of patients that better represent the real-world population, such as those with multiple myeloma who have renal dysfunction, Sidana concludes.

Surbhi Sidana, MD, discusses the unmet needs for patients with relapsed/refractory multiple myeloma who could be candidates for CAR T-cell therapy but have impaired renal function, and how clinical trials for these therapies have excluded this subset of patients.

Dr Sidana on CAR T-cell Therapy in Patients With R/R Myeloma and Renal Impairment

Surbhi Sidana, MD, assistant professor, medicine, Department of Medicine, Division of Blood and Marrow Transplantation & Cellular Therapy, leader, Myeloma Cellular Immunotherapy program, Stanford University School of Medicine, discusses the feasibility of administering idecabtagene vicleucel (ide-cel; Abecma) in patients with relapsed/refractory multiple myeloma with renal impairment.

A retrospective evaluation of real-world outcomes of patients with relapsed/refractory multiple myeloma included 211 patients who received standard-of-care ide-cel across 11 US centers in the US Multiple Myeloma CAR T Consortium, Sidana says. Of these patients, 28 had renal impairment, defined as a creatinine clearance of less than 50 mL/min at the time of CAR T-cell infusion, and 11 had severe renal impairment, defined as a creatinine clearance of less than 30 mL/min or being on dialysis at the time of CAR T-cell infusion, Sidana explains.

Adjusting the lymphodepletion doses is important in patients with renal impairment who receive fludarabine, Sidana notes. Although there was no dose reduction mandate since this was a retrospective analysis, 82% of patients with renal impairment received reduced doses of fludarabine, and 74% had over a 20% dose reduction, Sidana says.

Safety data regarding the rate and severity of cytokine release syndrome and neurotoxicity were similar between the patients with renal impairment and those with normal renal function, Sidana explains. Patients with renal impairment tended to have longer hospital stays and higher rates of grade 3 or higher cytopenias at day 30, but these rates became more similar between the 2 groups by day 90, Sidana notes.

Importantly, patients with renal impairment who received ide-cel also benefitted from this treatment, Sidana emphasizes. The overall response rates and median progression-free survival were comparable between the 2 groups, at 96% and 6.5 months, respectively, in patients with renal impairment vs 83% and 8.1 months, respectively, in those without renal impairment, Sidana says. Additionally, there were no differences in non-relapse mortality between the 2 groups, Sidana notes.

When assessing whether renal function changed over time in patients who received ide-cel, the investigators found that ide-cel did not make renal function worse in patients with renal impairment, and from baseline to day 30, no new patients with renal impairment needed dialysis, Sidana highlights.

It is feasible for patients with relapsed/refractory multiple myeloma with renal impairment to receive BCMA-directed CAR T-cell therapy, specifically ide-cel, Sidana concludes.

Surbhi Sidana, MD, discusses the feasibility of administering idecabtagene vicleucel in patients with relapsed/refractory multiple myeloma with renal impairment.

Surbhi Sidana, MD

Articles

Strategic Timing for CAR T in R/R MM: The Importance of Early Referral

Cilta-cel vs. Ide-cel: Key Data Updates and Clinical Decision-Making in R/R MM

Sequencing CAR T in More Heavily Pretreated R/R MM as well in patients who deferred initial autologous HSCT

Optimizing CAR T in R/R MM: Treatment Paradigms and Patient Selection

Dr Sidana on CAR T-cell Therapy in Patients With R/R Myeloma and Renal Impairment

Dr. Sidana on CAR T-cell Therapy in R/R Multiple Myeloma With Renal Impairment