Treatment Options and Sequencing for Late Relapsed/Refractory Multiple Myeloma

Late Relapsed/Refractory Multiple Myeloma Treatment Options

Cohosts of the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, met with myeloma specialist Maximilian Merz, MD, of Memorial Sloan Kettering Cancer Center, to discuss the treatment algorithm for late-line RRMM.

Multiple Myeloma Treatment Algorithms

The treatment paradigm for multiple myeloma shifted dramatically after quadruplet class regimens became the standard of care for frontline treatment. Patients are now quad-class exposed at first relapse, and several treatment options have shifted into earlier lines as a result. After progression on a frontline quadruplet therapy, anti-BCMA CAR T-cell or bispecific antibody therapies are preferred second- and third-line options. Ciltacabtagene autoleucel (cilta-cel) and teclistamab with or without daratumumab are currently approved in these early relapse settings. Notably, several CELMoDs under investigation are likely to be approved for the disease and may potentially affect multiple myeloma treatment settings.

If patients progress on cilta-cel and teclistamab, late relapse treatment options include additional anti-BCMA bispecific antibodies, talquetamab, selinexor, elotuzumab–based regimens, chemotherapy, and chemotherapy combinations. Talquetamab is a novel anti-GPRC5D bispecific antibody, while selinexor is a XPO1 inhibitor. Based on current data, Dr. Merz prefers to use CAR T-cell therapy at first relapse in eligible patients. He sequences subsequent treatment as follows: BCMA–directed bispecifics, talquetamab, chemotherapy–based treatment, and selinexor. Although elotuzumab–based regimens have fallen out of use in the late-relapse setting, they are occasionally used as a bridging therapy before CAR T-cell infusion, said Dr. Merz. 

Treatment Sequencing Considerations

Generally, CAR T-cell therapy is preferred before bispecific antibodies because prolonged bispecific therapy can impair T-cell function, which can make CAR T-cell manufacturing less viable. In addition, patients who progress on bispecific antibodies are more likely to lose target antigen expression compared with CAR T cells. Oncologists should retest for antigen expression or BCMA mutation when patients progress on an anti-BCMA therapy to determine if additional BCMA–targeted therapy would be effective, said Dr. Merz. If expression is lost, it typically does not return, and alternative treatment mechanisms are needed. 

Treatment-Related Toxicity in Late RRMM

Treatment for late RRMM carries distinct toxicities based on their mechanism of action and target biomarker. Increased infection risk, cytokine release syndrome, and neurotoxicities are key side effects of BCMA–directed therapies. Talquetamab is associated with distinct taste, skin, and nail changes that can have an outsize impact on quality of life. Chemotherapy regimens commonly result in cytopenias, while selinexor may cause nausea and vomiting that can be dose-limiting. Each treatment has a variety of supportive and prophylactic strategies to manage adverse events. 

When selecting treatment options after any relapse, oncologists should consider the patient’s age, comorbidities, prior treatments, duration of response to balance effective treatments with preserved quality of life, the doctors concluded.