Unpacking Data From Pivotal Trials in Multiple Myeloma: Lessons Learned From the MajesTEC-1 Trial of Teclistamab

In this third episode of OncChats: Unpacking Data From Pivotal Trials in Multiple Myeloma, Hamza Hashmi, MD, of the Medical University of South Carolina, highlights the efficacy and safety profile of teclistamab, a BCMA-directed bispecific T-cell engager, in heavily pretreated multiple myeloma.

The next trial that I would like to discuss is the MajesTEC-1 trial [NCT04557098]. The phase [2], single-arm study looked at teclistamab-cqyv [Tecvayli], which is BCMA-targeting bispecific T-cell engager, in patients with heavily pretreated relapsed or refractory multiple myeloma.

The trial enrolled patients who have had at least 3 prior lines of therapy, and have had exposure to daratumumab [Darzalex], a proteasome inhibitor, and an immunomodulatory agent. [Patients received a] medium of 6 prior lines of therapy. Patients had teclistamab given subcutaneously in a step-up manner on day 1, 4, and 7. After that, teclistamab was continued every week until disease progression or intolerable toxicity.

The trial had its results [shared at a] recent meeting; [data were] also published [in] a major journal. [We saw] that 66% of the patients achieved a response; at least half of these responses were very good partial remissions. Time to initial response was around 1 month, time to best response was around 4 months, and median duration of response was around 18 months. [Moreover, the] median progression-free survival on this trial was around 11 months. The median overall survival was around 18 months although the data remain immature at this time and [we need] longer follow-up.

Teclistamab [resulted in] very deep, and perhaps durable, responses in a heavily pretreated patient population [but it] was associated with some treatment-related adverse effects [AEs], notably cytokine release syndrome [CRS], which was seen in about 70% of the patients. The majority [of CRS cases were] grade 1 and 2, and only less than 1% were grade 3. One-third of these patients required tocilizumab [Actemra] for the management of CRS. Onset was early with the step-up doses and the duration was only around [2 days]. Immune cell effector–associated neurotoxicity syndrome, or ICANS, was seen in about 10% of the patients and less than 1% required management with dexamethasone. No grade 3 effects were seen.

A very common [AE] that was reported was cytopenias, [and this was experienced by] about two-thirds of the patients; this included neutropenia, anemia, and thrombocytopenia. These cytopenias were transient, usually [occurring] in the first couple of months and cycles and were manageable with supportive care and resolved spontaneously over time. Another very important, and perhaps the most relevant, clinical AE that was noticed was hypogammaglobulinemia; it was seen in about 70% of the patients, and at least one-third of these patients required intravenous immune globulin [IVIg] administration. Significant hypogammaglobulinemia translated into severe infections—especially COVID-19 infection, [which was] the leading cause of mortality [in the trial].

Teclistamab has been recently approved by the FDA for patients with relapsed or refractory multiple myeloma, who have had at least 4 prior lines of therapy and who have had exposure to an anti-CD38 monoclonal antibody, proteasome inhibitor, and an immunomodulatory agent, and who had progressive disease on their last line of therapy. [The agent] is approved with the REMS [Risk Evaluation and Mitigation Strategy] program, with the step-up dosing requiring in-patient stay for at least 1 week and availability of tocilizumab for management of CRS. [Because teclistamab is an] available off-the-shelf option for patients with relapsed or refractory multiple myeloma, it is a very desirable option. These patients may not have many other options available. Compared with CAR T-cell therapy, being available off the shelf and not requiring any leukapheresis, chemotherapy, or lymphodepletion, makes it perhaps a more desirable option for patients who have aggressive disease and cannot wait 6 to 7 weeks before they have CAR T cells infused. Having said that, it is a continuous treatment that is given every week for as long as patients are responding; that does entail some inconvenience and some financial toxicity.

AEs are manageable, including CRS and ICANS. Patients who are receiving teclistamab should receive IVIg for management of hypogammaglobulinemia and subsequent infections. Very importantly, [they] should receive Evusheld for COVID-19 in case they are planning to continue with teclistamab.

Check back next Wednesday for the next episode of this series.