Hematological and Non-Hematological Toxicities in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Who Responded to Daratumumab, Pomalidomide, and Dexamethasone (DPd)

Background: Daratumumab is a humanized IgGκ monoclonal antibody that targets CD38 with direct antitumor effects working in synergy with immunomodulatory agents (IMiDs) resulting in depletion of immunosuppressive T and B cells and clonal expansion of cytotoxic T cells. Daratumumab triplet regimens containing pomalidomide and dexamethasone (DPd) are an effective treatment option for patients with relapsed/refractory multiple myeloma (RRMM). We aimed to analyze the risk of hematological and non-hematological toxicities in RRMM patients that responded to DPd.

Methods: Patients with RRMM treated with DPd at the University of Kansas Health System between January 2015 and June 2022 were included in our analysis. DPd consisted of 28-day cycles of daratumumab 16 mg/kg intravenously vs 1800 mg subcutaneous (weekly for cycles 1 and 2, every 2 weeks for cycles 3-6, and every 4 weeks); pomalidomide 4 mg orally (PO) on Days 1-21, and dexamethasone 20 or 40 mg weekly until progression or intolerance. Responses were evaluated using the International Myeloma Working Group (IMWG) criteria. Hematological and non-hematological toxicities were graded using the common terminology criteria for adverse events (CTCAE) grading system. Patient and disease characteristics and safety and efficacy outcomes were summarized with descriptive statistics (Table 1).

Results: A total of 97 patients with RRMM were evaluated using electronic medical records (EMR). The overall response rate (ORR) was 74% (n=72), with partial response, very good partial response, complete response (CR), and stringent CR seen in 27%, 10%, 22%, and 15% of patients, respectively. Median progression-free survival (PFS) was 10.3 months (95% CI 8.7-19.6), median duration of response (DOR) was 15 (2-62) months, and median number of cycles in responders was 12 (2-58) cycles. The most common grade III/IV hematological toxicities in those who responded to treatment were neutropenia (79%), leukopenia (65%), lymphopenia (56%), anemia (18%), and thrombocytopenia (8%). The most common cause of grade III/IV for non-hematological toxicities were pneumonia (17%) and peripheral neuropathy (8%) (Table 2). Dose reduction/interruptions rate were seen in 70% (50/72) of the patients, due to hematological toxicity in 75% and peripheral neuropathy in 15% of the patients. Hospitalization occurred in 27% of patients, with pneumonia being the most common reason (46%). The most frequent cause of treatment discontinuation was disease progression in 51/72 (70%) of patients. Treatment-related mortality was reported in 2% of patients, with pneumonia being the most common cause of death.

Conclusion: Patients who responded to DPd have a high risk of dose reduction and interruption rate secondary to hematological toxicities and a significant risk of hospitalization due to pneumonia. Further prospective studies are needed to evaluate the implementation of prophylactic antibiotics and the possible use of prophylactic granulocyte colony-stimulating factor in those with high-risk of infection to decrease the incidence of hospitalizations.