-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3605 Hematological and Non-Hematological Toxicities in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Who Responded to Daratumumab, Pomalidomide, and Dexamethasone (DPd)

Program: Oral and Poster Abstracts
Session: 905. Outcomes Research—Lymphoid Malignancies: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, Plasma Cell Disorders, Diseases, real-world evidence, Therapies, Lymphoid Malignancies, Adverse Events
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Polina Bellman, MD1, Wei Cui, MD2,3*, Zahra Mahmoudjafari, PhD2,4*, Shebli Atrash, MD2,5, Barry Paul, MD, MS2,6, Hamza Hashmi, MD2,7, Rajesh Banderudrappagari8*, Leyla O. Shune, MD9,10, Al-Ola Abdallah, MD10,11 and Nausheen Ahmed, MD2,12

1University of Kansas Medical Center, Kansas city, KS
2US Myeloma Research Innovations Research Collaborative (USMIRC), Westwood, KS
3University of Kansas Medical Center, Kansas City, KS
4Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS
5Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC
6Plasma Cell Disorders Section, Department of Hematologic Oncology & Blood Disorders, Levine Cancer Institute, Carolinas Healthcare System, Charlotte, NC
7Department of Hematology/Medical Oncology, Medical University of South Carolina, Charleston, SC
8CoxHealth, Springfield, MO
9The University of Kansas Medical Center, Kansas City, KS
10US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS
11Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Westwood, KS
12Division of Hematologic Malignancies & Cellular Therapeutics, The University of Kansas Cancer Center, Westwood, KS

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.

Disclosures: Mahmoudjafari: Incyte: Membership on an entity's Board of Directors or advisory committees; Merk: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Atrash: Takeda: Honoraria; Sanofi: Honoraria, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Honoraria, Research Funding; Celgene: Honoraria, Speakers Bureau; Amgen: Research Funding. Paul: Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees; Regeneron: Membership on an entity's Board of Directors or advisory committees. Hashmi: Sanofi: Consultancy, Speakers Bureau; GSK: Speakers Bureau; KARYOPHARM: Speakers Bureau; JANSSEN: Consultancy; BMS: Consultancy.

*signifies non-member of ASH