Background: Multiple myeloma (MM) accounts for approximately 10% of all hematologic malignancies and the median age of patients at diagnosis is about 69 years of age. MM therapies with various mechanisms of action have been approved. Bispecific T-cell engager antibodies (BsAbs) are a relatively new class of therapy for this hematologic malignancy.
Elranatamab-bcmm, talquetamab-tgvs, and teclistamab-cqyv are BsAbs currently approved for treatment of relapsed refractory MM based on single arm trials. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are important adverse reactions (ARs) that require close monitoring and potential intervention. Other symptomatic ARs including gastrointestinal disorders and skin disorders are experienced by patients, related to the BsAb target.
Patient-reported outcomes (PROs) are a measurement based on a report that comes directly from the patient about the status of their health without interpretation from a clinician or anyone else. We examined existing safety information to identify common symptoms that could be assessed using PROs.
Methods: We reviewed the US Prescribing Information (USPI) for BsAbs approved for MM accessed using the Drugs@FDA database. We examined rates of symptomatic ARs using information from Section 5 (Warnings and Precautions) and Section 6 (Adverse Reactions) of each USPI. All symptomatic ARs were reviewed, with a focus on ARs occurring in more than 20% of patients. Given our focus on symptomatic ARs, we excluded those that required laboratory or radiologic confirmation, thereby excluding ARs such as infections. We reviewed protocol information about the BsAb registrational trials available through clinicaltrials.gov.
Results: Median age of patients enrolled in each trial was 68 years for elranatamab-bcmm, 64 years for teclistamab-cqyv, and 67 years for talquetamab-tgvs. A substantial percentage of patients experienced CRS (58% elranatamab-bcmm, 72% teclistamab-cqyv, 76% talquetamab-tgvs). Neurologic toxicity occurred in the majority of patients (59% elranatamab-bcmm, 57% teclistamab-cqyv, 55% talquetamab-tgvs), with headache being most common. Gastrointestinal disorders were also common, with diarrhea (36% elranatamab-bcmm, 21% teclistamab-cqyv, 21% talquetamab-tgvs) and nausea (22% elranatamab-bcmm, 25% teclistamab-cqyv, 18% talquetamab-tgvs) occurring in BsAb treated groups. Side effects such as fatigue and musculoskeletal pain occurred in >30% of patients treated with BsAbs. Patients who received talquetamab-tgvs experienced high rates of dysgeusia (70%), dry mouth (34%), xerosis (30%) and dysphagia (23%). Injection site reactions occurred in 37% of patients with elranatamab-bcmm and teclistamab-cqyv).
We found that in all three registrational BsAbs trials examined, fixed PRO questionnaires (e.g., EORTC QLQ-C30) were used, and no trial included symptoms selected from an item library.
Conclusion: Given that patients with MM are typically older than populations treated for other hematologic malignancies, tolerability is an important consideration. Assessment of BsAb tolerability in patients with relapsed refractory MM is important as patients with this condition are likely to (1) have residual side effects from prior lines of therapy, (2) have comorbid and pre-existing conditions related to age, and (3) be treated with BsAbs until disease progression or unacceptable toxicity, potentially enduring long periods of side effects.
As described above, BsAbs have a unique side effect profile, which is not completely covered by commonly used fixed PRO questionnaires. Our analysis is not meant to compare incidence or severity of symptomatic ARs between BsAbs, rather to identify common symptoms that would be important to assess in BsAb trials. Rigorous assessment of PROs can provide complementary information regarding the tolerability of BsAbs. Although incidence and severity of these ARs are described in the USPI, additional efforts are required to understand the onset, trajectory, and duration of these symptoms. Further work should be done to identify the most relevant patient-reported symptoms available in PRO item libraries to deploy in MM BsAb trials to complement traditional safety information.
No relevant conflicts of interest to declare.
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