Monitoring and Managing CAR T-Cell Therapy in Multiple Myeloma

Tiffany Richards, PhD, APRN, ANP-BC, AOCNP, reviews a case of a 65-year-old woman with high-risk, relapsed/refractory multiple myeloma who achieved a stringent complete response following sequential CAR T-cell therapies, including a GPRC5D-targeted product. She highlights key clinical decision-making across multiple lines of therapy and emphasizes early recognition and management of CAR T–related toxicities such as cytokine release syndrome, cytopenias, neurocognitive changes, and dysgeusia.

The discussion provides practical guidance on supportive care strategies, including infection prophylaxis, IVIG replacement, growth factor support, and symptom management. The case underscores the importance of ongoing laboratory monitoring—particularly ferritin, C-reactive protein, and CD4 counts—to optimize patient safety and long-term outcomes during and after CAR T-cell therapy.

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Transcript:

Hi, I am Tiffany Richards, and I am a nurse practitioner at the University of Texas MD Anderson Cancer Center. I work in the department of lymphoma and myeloma, specifically focusing on patients with plasma cell dyscrasias. We are going to review a case study of a patient with relapsed/refractory multiple myeloma.

She is a 65-year-old woman who initially presented back in 2017 with pancytopenia as well as pain to her sternum. She underwent a bone marrow biopsy at the time and was found to have 70% kappa restricted plasma cells, and she was found to have a deletion of 17p at the time. She was also anemic with a hemoglobin of 7.8. Her β2 microglobulin (β2M) was actually within the normal range at 2.3. Albumin was 3.2. She had an elevated IGA of 4750, an elevated kappa light-chain of 1181, and she had 1.9 grams of kappa Bence-Jones proteinuria. She also had an IGA kappa M protein of 5.3. 

And so she was diagnosed with symptomatic multiple myeloma with revised International Staging System stage 2 disease based on her β2M, albumin, and her deletion of 17p. She was initially started at an outside institution on bortezomib, lenalidomide, and dexamethasone, and subsequently presented to our center where, because of her high-risk disease, her therapy was changed to carfilzomib, lenalidomide, and dexamethasone. She achieved a partial response and went on to autologous stem cell transplant on a clinical trial with busulfan and melphalan.

Post-transplant, she actually was placed on a clinical trial with elotuzumab and lenalidomide. It was a maintenance study that we had at the time, and she was on this for quite a bit of time, about 26 months before she developed a biochemical progression. And because of her high-risk disease, we did change her treatment to daratumumab, pomalidomide and dexamethasone. She remained on this for over a year and subsequently developed disease progression and had alternating periods of remission and progression and received a total of 5 additional lines of therapy. 

She then went on to a CAR T-cell trial with Bb2121 and actually achieved a complete response and was followed on observation. However, she then relapsed about 18 months later and was placed on therapy with cetuximab, pomalidomide, and dexamethasone. And our reasoning behind that was it had been a significant period of time since she had a CD3 monoclonal antibody. She unfortunately did not have a response to that. 

In order to get a disease response, we did change her to selinexor, pomalidomide, and dexamethasone and she actually responded well to that. And at the time we had a CAR T-cell trial that targets GPRC5D and so she went on to that and she was bridged with venetoclax and dexamethasone and achieved a very good partial remission and went on to receive her CAR T-cell products.

She was infused on day 0, however day 2 she developed fevers post-cell infusion and this persisted through day 4 and her ferritin actually went from 121 on day 1 all the way up to 2375 on day 7. She also did have an elevation in her C-reactive protein, which is very common with CAR T-cell therapies. And so that's why we check ferritins and C-reactive proteins daily so we can monitor that and keep a close eye. That also helps us when we're looking at if she would develop ICANS or any other symptoms. 

When she developed her fever, she was placed on IV antibiotics just because you don't want to automatically assume that because somebody has a fever that it's CRS. We do cover for infection. Her cultures were negative, but because of her persistent grade 1 CRS, she did receive tocilizumab and she received a total of 3 doses on days 4 and 5.

Interestingly enough, she did have some visual hallucinations, and it was felt that it was due to cefepime and so that was discontinued and her antibiotic was changed. Because she had the visual hallucinations, a CT of the head and the EEG were checked and these were normal. Once the antibiotics were changed, her hallucinations did stop. And I would say that when somebody is having changes in mentation, we also need to make sure that we're ensuring that this isn't due to ICANS. 

And so, she had no other changes in her CARTOX, that all remained stable, and so it was not felt that those visual hallucinations were due to ICANS. She was subsequently discharged and followed on observation. However, she did have some persistent neutropenia that lasted about 2 months post- her cell infusion and that is something that we can see post-CAR T-cell therapy. And so she did require intermittent growth factor support for that.

She also had some dysgeusia. GPRC5D, and some of you may be familiar with talquetamab which targets the same receptor, is expressed on the taste buds. And so, because of the dysgeusia, we did start her on zinc gluconate and we tried some other interventions that really didn't work. Thankfully, her dysgeusia started to improve around 4 months post-cell infusion but did continue to persist. She initially lost about 17 lbs but then slowly gained that weight back over a 2-month period of time. 

Post-CAR-T, we do place patients on IVIG monthly and we also placed them on pneumocystis pneumonia (PJP) prophylaxis and so she was on that as well. She's remained in a stringent CR and has remained negative on minimal residual disease. And so, this has been about 6 months now post- her CAR T-cell infusion and she's doing well. So given that she is now 6 months post- her CAR T-cell infusion, we do also monitor the CD4 count and so we monitor that every month. And once a CD4 count goes above 200 and they're more than 6 months post-CAR T-cell infusion, then we can consider stopping the prophylaxis for PJP. So that's another important lab that we need to be monitoring in patients who are post-CAR T-cell therapy. The other thing that I would add in patients undergoing CAR T-cell therapy is that it is recommended for them to receive their immunizations all over again, similar to what we do in patients who've undergone autologous stem cell transplant.

I think this case really highlights the importance of monitoring of blood counts, CRP and ferritin in the initial stages of CAR-T. It highlights the interventions that are important when a patient develops fevers, so not only covering for CRS but also fevers. And I think it also highlights that when, depending on the target, we do need to think about other off-target effects that can happen with our CAR T-cell products.

Our clinical question is what lab monitoring is required while a patient is undergoing CAR T-cell therapy? One, ferritin, two, C-reactive protein, three, CD4 count, or four, all of the above. The correct answer is going to be all of the above. We monitor the ferritin and the C-reactive protein really just in the initial post-infusion while the patient's in the hospital or if they're receiving it outpatient for monitoring of CRS and ICANS. We monitor the CD4 count once a month. And so really, the lab monitoring for a patient who is undergoing CAR T-cell therapy is going to be all of the above because all 3 of those labs are important to be following.