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CARVYKTI Shows OS Benefit
According to the research linked below, CARVYKTI shows OS benefit when compared to current standard-of-care therapies for RR/MM patients.
Why then, does Dr. Mohyuddin, (an assistant professor in the multiple myeloma program at Huntsman Cancer Institute) say “the trial does not change my practice.”
There are two reasons why.
- First, the clinical trial compares CARVYKTI to inferior RR/MM therapies and
- Second, CAR-T therapies brings with it the risk of serious side effects.
Though the RR/MM patient may be running out of therapy options, there may be options available to them. CAR-T cell therapy has great potential but the study below does not cite CARVYKTI as a viable option.
Further, if the RR/MM patient does choose to undergo CAR-T cell therapy, they must understand the risk of many serious short and lone-term side effects.
What are the short and long-term side effects of of CARVYKTI CAR-T cell therapy for RR/MM patients?
Short-Term Side Effects
These typically occur within days to weeks after the infusion of CARVYKTI and can include:
- Cytokine Release Syndrome (CRS):
- CRS is the most common side effect of CAR-T cell therapy, occurring in a majority of patients. It is caused by the release of large amounts of cytokines (immune system proteins) from the activated T cells.
- Symptoms: High fever, fatigue, nausea, low blood pressure, difficulty breathing, rapid heart rate, and multi-organ dysfunction in severe cases.
- Onset: Usually within the first week, typically around days 7–10 post-infusion.
- Management: CRS is often treated with tocilizumab (an anti-IL-6 receptor antibody) and steroids.
- Neurotoxicity (ICANS – Immune Effector Cell-Associated Neurotoxicity Syndrome):
- Neurotoxicity, which includes confusion, difficulty speaking, seizures, and encephalopathy, is another significant short-term risk.
- Symptoms: Headaches, tremors, confusion, delirium, difficulty writing or speaking, and in rare cases, coma.
- Onset: Typically occurs within a week to two after the CAR-T infusion.
- Management: Corticosteroids and other supportive care measures.
- Infections:
- The immune system is suppressed following CAR-T therapy, increasing the risk of infections.
- Bacterial, viral, and fungal infections are common, especially early post-treatment when patients are still recovering from the chemotherapy used for lymphodepletion prior to the CAR-T cell infusion.
- Low Blood Counts:
- Patients often experience prolonged cytopenias (low levels of red and white blood cells, and platelets) following CAR-T therapy. This can lead to anemia, increased risk of infections (due to neutropenia), and bleeding complications.
- Recovery from cytopenias can take weeks to months.
- Fatigue:
- Severe fatigue is common and can persist for several weeks following treatment.
- Hypogammaglobulinemia:
- A reduction in normal antibody levels can occur due to the targeting of B cells, which are involved in antibody production. This increases susceptibility to infections.
Long-Term Side Effects
Long-term side effects may persist for months to years after CARVYKTI infusion.
- Persistent Cytopenias:
- While cytopenias are a short-term side effect, in some patients, these can persist long-term, especially for those who have undergone extensive prior therapies that may have already weakened their bone marrow.
- Secondary Malignancies:
- Although rare, there is a potential long-term risk of developing secondary cancers after CAR-T therapy due to the genetic modifications made to the T cells. This risk, however, remains under study, and long-term follow-up is needed.
- Hypogammaglobulinemia (chronic):
- Long-term hypogammaglobulinemia may require immunoglobulin replacement therapy to help prevent recurrent infections.
- Reactivation of Viral Infections:
- Immunosuppression from CAR-T therapy can lead to the reactivation of latent viruses, such as cytomegalovirus (CMV) or Epstein-Barr virus (EBV).
- Chronic Fatigue and Neurological Issues:
- Some patients may experience prolonged fatigue and lingering neurological symptoms, including mild cognitive deficits or mood changes, although these tend to improve over time in most cases.
- B Cell Aplasia:
- CAR-T cell therapy may cause long-term B cell aplasia, where B cells (responsible for antibody production) are reduced or absent, potentially necessitating regular immunoglobulin replacement therapy for infection prevention.
Let me be clear. CAR-T cell therapy holds great promise for relapsed, refractory myeloma patients. Highlighting the fact that CARVYKTI shows OS benefit is important. However, it is also important for MMers to understand the possible risks and rewards of any new therapy.
Are you consindering CAR-T cell therapy? Are you relapsed, refractory? Email me a David.PeopleBeatingCancer@gmail.com if you’d like to learn moore about both conventional and non-conventional MM therapies.
Thank you,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
CARTITUDE-4 Update: Cilta-Cel Improves OS in R/R MM
“A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel, or cilta-cel (CARVYKTI), reduces the risk for death by 45% vs standard-of-care (SoC) therapies in patients with lenalidomide-refractory multiple myeloma, according to the latest data from the phase 3 CARTITUDE-4 study…
A prespecified overall survival (OS) analysis at a median follow-up of 34 months showed that median OS was not reached in either the cilta-cel or SoC therapy arm (hazard ratio [HR], 0.55). The 30-month OS rates were 76% and 64% in the arms, respectively, said Mateos, a professor at the University Hospital of Salamanca, Salamanca, Spain…
The US Food and Drug Administration first approved cilta-cel in 2022 for use after at least four prior lines of therapy in patients with lenalidomide-resistant multiple myeloma based on findings from the CARTITUDE-1 trial. In April 2024, based on progression-free survival (PFS) findings at median follow-up of 16 months in CARTITUDE-4 (HR for progression/death vs SoC, 0.26), that approval was expanded to include patients with lenalidomide-refractory multiple myeloma after one or more prior lines of therapy…
“The trial does not change my practice,” said Mohyuddin, an assistant professor in the multiple myeloma program at Huntsman Cancer Institute, University of Utah, Salt Lake City…
“We must recognize that the control arm [in CARTITUDE-4] isn’t the best available standard of care,” he explained, noting that carfilzomib-containing triplets were not allowed. “Furthermore, overall survival is dependent on access to good therapies upon relapse, and patients in the control arm did not cross over to get cilta-cel at the time of relapse.
“We do not know if overall survival benefit would have been present if the control arm was better and if there was access to better post-protocol therapy.”
Toxicity is also a concern, he said.
“I think of it as high risk-high reward. There was a sevenfold increased incidence of secondary hematological malignancies in the cilta-cel arm compared to standard of care — this is a very concerning signal that dampens my enthusiasm to use this drug early for everyone,” he added.
For example, although Parkinsonism was rare, it generally did not resolve and lasted years, resolving in only 13% of affected patients, with a median time to resolution of 523 days.
“These are horrible odds, and for many patients there may be safer options,” he noted, adding that “cilta-cel is an option I would consider for some relapses (very early relapse while still on multi-agent therapy, high-risk disease), but otherwise I think personally it’s too toxic for most first relapses.””