NSO-07: Management Considerations for Dermatologic Toxicities Associated With Talquetamab, a GPRC5D×CD3 Bispecific Antibody, in Patients With Relapsed/Refractory Multiple Myeloma

Introduction: Talquetamab is a T-cell redirecting bispecific antibody that targets a novel antigen, GPRC5D, on myeloma cells. Data from the MonumenTAL-1 study in patients with relapsed/refractory multiple myeloma (RRMM) showed overall response rates of >71% and durable responses at talquetamab weekly (QW) and every other week (Q2W) dosing. Talquetamab is associated with a distinct group of GPRC5D-related adverse events (AEs), including dermatologic (skin and nail) AEs. Here we describe the presentation and management of dermatologic AEs in patients from MonumenTAL-1 treated at a single center.

Methods: MonumenTAL-1 (NCT03399799/NCT04634552) is an open-label, single-arm, phase 1/2 study of patients who had progressed on or could not tolerate established MM therapies (phase 1) or were exposed to ≥3 prior lines of therapy (phase 2; including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody). Patients included in the current analysis received subcutaneous talquetamab at the recommended phase 2 doses (RP2Ds) of 0.4 mg/kg QW or 0.8 mg/kg Q2W. AEs were graded according to CTCAE v4.03.

Results: Talquetamab has demonstrated 12-month PFS rates of 35% and 54% and OS rates of 76% and 77% with QW and Q2W dosing in the MonumenTAL-1 study. Dermatologic AEs in MonumenTAL-1 included skin (eg, dry skin, exfoliation), rash, and nail (eg, thinning, peeling) AEs. Among patients (N=24) receiving the talquetamab RP2Ds in our center, 87.5% had skin (grade 3, 4.2%), 45.8% had rash (grade 3, 33.3%), and 58.3% had nail (grade 3, 0%) AEs. Median time to onset of dermatologic AEs was ~4.6–15 weeks following first talquetamab dose. Most dermatologic AEs resolved, except nail AEs: only 28.6% of events resolved, with a median time to resolution of ~16 weeks; this is potentially due to timing of nail regrowth. Management of dermatologic AEs included a heavy moisturizer for general dryness; ammonium lactate 12% lotion twice daily (BID) for hand and foot peeling; loratadine 10 mg oral tablet daily for 3–5 days post dose and triamcinolone 0.1% cream BID for pruritus, injection-site reaction, and rash; and nail hardeners, topical vitamin E oil, and triamcinolone 0.025% ointment for nail thinning and peeling. Methylprednisolone taper and betamethasone 0.05% cream BID were considered for grade 3 rash. Other grade 3 dermatologic AE mitigation approaches included dose holds. In general, patients were encouraged to take short lukewarm showers, use a heavy lotion or moisturizer throughout the day on skin and cuticles, and keep nails short and clean. Patients considered the AEs generally tolerable, and no patient from our center discontinued the study due to dermatologic AEs.

Conclusions: Talquetamab is an effective therapy for patients with RRMM. Skin and nail AEs are common but are primarily low grade with no discontinuations. Appropriate management, education, and supportive care ensure that patients can stay on treatment to receive optimal benefit from talquetamab.