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Multiple Myeloma an incurable disease, but I have spent the last 25 years in remission using a blend of conventional oncology and evidence-based nutrition, supplementation, and lifestyle therapies from peer-reviewed studies that your oncologist probably hasn't told you about.
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CAR-T Non-Relapse Deaths
CAR-T Non-relapse deaths are a serious concern, at least in my experience as an MM survivor. According to the study linked below, 8.0 percent of MM CAR-T survivors die from CAR-T cell “non-relapse mortality” rather than from MM itself.
Having said the above, I quickly follow up by saying that CAR-T cell therapy can be a lifeline to the MM patient who has relapsed and become refractory to other MM treatments.
When I underwent an autologous stem cell transplant, I knew that I was taking a risk. In fact, I even signed forms releasing my hospital from liability. But there lies the problem. The ASCT that I underwent in 1995 was clearly riskier than I was told. ASCTs are said to be “potentially curative…”
The same can be said for MM patients considering CAR-T cell therapy.
Further, studies have been published indicating that the MM patient’s age, immune system, frailty, and microbiome health can all play a significant role in how the patient does after CAR-T cell therapy.
Whether it’s an ASCT or CAR-T cell therapy for MM, research has shown that patients do better when undergoing a host of complementary therapies. Unfortunately, these therapies are not “FDA approved.”
An analysis of non-relapse mortality after CAR-T therapy in patients with lymphoma and myeloma
How much should your oncologist tell you about the risks you’re taking on with CAR-T cell therapy?
Please scroll down the page and let me know what you think.
Thank you,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Deaths Among Cancer Patients on CAR-T Therapies: New Study Probes Nonrelapse Causes
Although most patients who undergo CAR T-cell therapy ultimately die because of underlying disease, a subset of patients die from nonrelapse mortality (NRM) related to complications from the treatment. About half of those nonrelapse deaths among patients treated with CAR-T for lymphoma or multiple myeloma were attributed to infections, results of a recent study showed.
“NRM, in terms of the toxicity of CAR T-cell therapy, is the most devastating complication that can occur,” study author Kai Rejeski, MD, of Memorial Sloan Kettering Cancer Center in New York City, told Oncology News Central. “It is a complication that resulted in the death of the patient and is something we take very seriously.”
In this analysis, Dr. Rejeski and colleagues performed a systematic review and meta-analysis of reported NRM after CAR T-cell therapy in patients with lymphoma and multiple myeloma up to March 2024. Their search identified a total of 7,604 patients across 18 clinical trials and 28 real-world studies, with 574 nonrelapse deaths reported.
Notably, most of the included studies did not report cumulative incidence rates of NRM. Thus, the authors derived NRM point estimates using random effect models. The NRM point estimate across all included studies was 6.8% overall, indicating that about 1 in 15 patients died from a nonrelapse-related cause. These NRM estimates varied across disease entities and were highest among patients with mantle cell lymphoma (10.6%), followed by multiple myeloma (8.0%), large B-cell lymphoma (6.1%), and indolent lymphoma (5.7%).
More than half (50.9%) of the 574 nonrelapse deaths were attributed to infections, followed by other malignancies (7.8%) and cardiovascular or respiratory events (7.3%). CAR-T therapy–specific toxicities, such as immune effector cell-associated neurotoxicity syndrome (ICANS)/neurotoxicity, cytokine release syndrome (CRS), and hemophagocytic lymphohistiocytosis (HLA), accounted for 11.5% of NRM.
“What we found is that toxicities like ICANS, CRS, and HLA, which are rare but serious complications, are not the complications that CAR T-cell recipients are succumbing to,” Dr. Rejeski said. “Instead, it is infection complications…”
Looking at it optimistically, these data indicate that successful management of CRS and ICANS has decreased the effect of these toxicities on NRM, Dr. Rejeski said. However, the results indicate that the field must better characterize infectious complications associated with CAR T-cell therapy…
Dr. Jain agreed, stating that “manuscripts such as these are bringing greater attention to infectious risks.”
“We do not yet know which interventions will be successful to prevent these infections,” Dr. Jain said. “Some possibilities include the use of prophylactic antibiotics, increased use of antibody replacement infusions (termed IVIG), or other strategies. In general, some patients have poor recovery of their immune system after CAR-T – poor immune reconstitution – and as a field, we need to work on strategies to improve patients’ immune reconstitution after CAR-T.”
Dr. Rejeski also noted that the study found that axicabtagene ciloleucel for large B-cell lymphoma and ciltacabtagene autoleucel for multiple myeloma were independently associated with increased NRM point estimates.
“NRM is only one of many factors that will underly choices of one CAR T-cell product versus another, including differences in efficacy, logistics, or cost.” Dr. Rejeski said. “However, knowing one product is associated with higher NRM may push us to choose one versus another, particularly in older or frail patients with a lot of comorbidities.”
Dr. Rejeski reported research funding, consultancy, honoraria, and travel support from Kite/Gilead; honoraria from Novartis; consultancy and honoraria from BMS/Celgene; and travel support from Pierre-Fabre.
Dr. Jain reported consultancy/advisory funding from Kite/Gilead and Novartis and research funding from Kite/Gilead, Incyte, and Loxo@Lilly.
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