When to Raise the Question of CAR T-Cell Therapy in Multiple Myeloma

Samantha Shenoy, NP, and Caitlin Costello, MD, discuss how risk stratification, early relapse patterns, and changes in disease trajectory can help oncology care teams recognize when a patient with multiple myeloma may warrant consideration for cellular therapy, including CAR T-cell therapy. The episode highlights the role of nurses and advanced practice providers in identifying clinical shifts and supporting timely multidisciplinary discussion.

Moderator: Welcome to Oncology Learning Network. I'm Jenny Lamberts.  In this episode, we are exploring a question that comes up in myeloma care every day. How do we know when a patient's disease course should prompt a conversation that includes cellular therapy? To discuss this, I'm joined by two faculty members deeply embedded in the day-to-day practice of multiple myeloma care. Samantha Shenoy is a nurse practitioner at the University of California, San Francisco Medical Center, where she has spent 17 years caring for patients with multiple myeloma with a focus on immunotherapy, including CAR T-cell therapy. Caitlin Costello is a clinical professor of medicine and director of the myeloma program at the University of California, San Diego. Together, they discuss how evolving treatment goals, risk stratification, and early relapse patterns can inform when a broader multidisciplinary conversation, including consideration of cellular therapy, may be warranted. Our focus today is on how clinical context, including risk features, response patterns, and disease trajectory, can help the multidisciplinary team recognize when a patient's course may warrant further discussion or referral consideration. This content is intended to support oncology nurses, advanced practice providers, and care team members in their day-to-day practice. 

Samantha Shenoy: So, when thinking about multiple myeloma, one of the things that we talk about is something called risk stratification, and risk stratification at diagnosis really matters, and it matters throughout the disease course. And there are frameworks like something called mSMART, and that basically helps to identify patients whose biology makes early relapse and drug resistance more likely. High-risk features, including deletion 17p or TP53 mutation, are associated with shorter remissions, more aggressive relapse patterns, and often less durable responses to conventional therapy. NCCN guidelines explicitly recognize cytogenetic risk factors as a factor in treatment planning and monitoring intensity and underscore that risk stratification has practical implications for how aggressively we follow these patients. At my practice, the nurse practitioners often order bone marrows. At your practice, you may not be the one ordering bone marrow and FISH cytogenetics, but it's still really important that you understand what the different cytogenetic abnormalities are and what their implications are. So, for example, if something's higher risk, just be aware of that and keep that in mind as you're caring for these patients. 

Moderator: Caitlin, can you build on that point? How do you connect risk stratification to what it means for treatment goals overall? 

Caitlin Costello: Not all myelomas are the same. We know that this requires a highly personalized approach to treatment for each patient. And I think it's important to put that in the historical context to say we used to use these therapies to treat all patients with the intent of some amount of disease control. And what we realized is that different therapies work differently for different patients. And so our goal has now been to get effective therapies to the right person at the right time to get that disease under control. And what control used to mean was for a short period of time, really now means deep and durable responses where, for all intents and purposes, we're kind of kicking the can down the road as far as we can until really the next newest and greatest comes up. So, when we're thinking about how to do that, CAR T-cells have such an important role here. As mentioned, we used it at very late stages of disease when patients had perhaps no other available therapies. But NCCN guidelines do not currently offer cellular therapy as an option for patients at the time of first relapse.  There's more and more interest in trying and re-stratifying, just as you mentioned, Sam, to say maybe not everybody needs CAR-T at the time of first relapse, but maybe there are some with high-risk disease that very much should have a CAR-T earlier. And maybe we think about the biology of the disease as much as the kind of health of the patient, thinking about whether we can have a prime opportunity to do CAR-T when a patient has healthier T cells, maybe has had fewer lines of therapy before, maybe they have a better functional status, where CAR-T could also be not only more effective but safer. 

Moderator: Samantha, how do the NCCN guidelines now frame the relapse-refractory pathway, and what does that mean for cellular therapy entering the conversation? 

Samantha Shenoy: NCCN guidelines now include relapsed/refractory myeloma pathways that account for prior lines of therapy and disease characteristics, providing a framework in which cellular therapy options are increasingly positioned as appropriate treatment options for patients. These patients, as you mentioned, may not be responding to therapy as we'd hoped, so this pattern is where the conversation about evaluating different treatment options, including cellular therapies, can and should start. 

Jenny Lamberts: Before we hear from the faculty about the advanced practice provider's role, it's worth pausing on a practical question. What does early relapse actually look like in the clinic? The signals worth paying attention to often appear before a formal progression assessment, such as an M-protein or free light chain that plateaus rather than continuing to fall. A patient returning earlier than expected with new bone pain, fatigue, or a new infection. Lab trends such as rising creatinine, new anemia, or dropping platelets that don't fit the expected post-treatment pattern, or simply a patient who says, "Something just feels different." Early relapse carries a distinctly poor prognosis and is recognized as a meaningful clinical trigger. For high-risk patients, progression from 12 to 18 months is a signal to pause and ask whether something different should be on the table. 

Caitlin Costello: I have some wonderful takeaways that I think you've offered up here today, which, number one, two, and three, are very much about how grateful and appreciative I am of my APPs, who really are kind of just my right-hand people in offering our patients the best care. You are often the person who notices when a clinical course isn't tracking as expected and can really help highlight the importance of a team approach to making sure we're taking care of these patients and offering the best personalized therapy for each patient. 

Moderator: Samantha, can you put a finer point on what that looks like day-to-day and what an APP actually needs to do when they notice a shift in patterns? 

Samantha Shenoy: At our practice, the APPs are seeing patients more frequently and for longer than the attending physician. I know that, as an attending physician, you're running around doing a million things, and because of that, we are following them more closely and are often the first to notice when something's shifted. So, it's really important, as an APP, to recognize the patterns indicating that this is a high-risk disease. Is this someone who's had a suboptimal response to therapy, or are they an early progressor? And then flagging it and then bringing it back to the team to start these conversations early. And as an APP, it's not our role to necessarily recommend that they start a specific therapy, but really all you need to do is ask the question: "Is this a patient that we should be discussing at our next tumor board? Is this someone who might benefit from evaluation at a CAR-T treatment center if you're not working at a CAR-T treatment center? And if you are, is this someone that we should consider CAR-T?" 

Moderator: As we close, three themes stand out from this discussion. First, treatment goals in myeloma have evolved. The depth and durability of the response matter, and a suboptimal response is a clinical signal. Second, risk stratification tools like mSMART, combined with early relapse patterns, can help identify patients who may benefit from earlier consideration of cellular therapy options. Third, in many myeloma practices, advanced practice providers and nurses see patients more frequently and over longer periods than the attending physician. Recognizing when a clinical course isn't tracking as expected and raising that question within the care team is a meaningful contribution to ensuring patients receive timely evaluation. This content is brought to you by Oncology Learning Network. For more expert perspectives and educational resources, visit oncologylearningnetwork.com. 

1. Beaupierre A, Lundberg R, Marrero L, Jain M, Wang T, Alencar MC. Management across settings: an ambulatory and community perspective for patients undergoing CAR T-cell therapy in multiple care settings. Clin J Oncol Nurs. 2019;23(2):27-34. 
2. Kumar SK, Rajkumar V, Kyle RA, et al. Multiple myeloma. Nat Rev Dis Primers. 2017;3:17046. doi:10.1038/nrdp.2017.46. 
3. Kumar SK, Therneau TM, Gertz MA, et al. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79(7):867-874. doi:10.4065/79.7.867. 
4. Lahuerta JJ, Paiva B, Vidriales MB, et al. Depth of response in multiple myeloma: a pooled analysis of three PETHEMA/GEM clinical trials. J Clin Oncol. 2017;35(25):2900-2910. doi:10.1200/JCO.2016.69.2517. 
5. Mikhael JR, Dingli D, Roy V, et al. Mayo Clinic. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013;88(4):360-376. doi:10.1016/j.mayocp.2013.01.019. 
6. Munshi NC, Avet-Loiseau H, Anderson KC, et al. A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma. Blood Adv. 2020;4(23):5988-5999. doi:10.1182/bloodadvances.2020002827. 
7. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 5.2026. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1445 Accessed 2026. 
8. Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-567. doi:10.1002/ajh.25791. 
9. Rajkumar SV, Kumar S. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc. 2016;91(1):101-119. doi:10.1016/j.mayocp.2015.11.007.