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3244 Clinical Features and Survival Outcomes in Diabetic Patients with Newly Diagnosed Multiple Myeloma (NDMM) Enrolled in the Connect® MM Registry

Program: Oral and Poster Abstracts
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation: Poster III
Hematology Disease Topics & Pathways:
Diseases, Plasma Cell Disorders, Lymphoid Malignancies
Monday, December 7, 2020, 7:00 AM-3:30 PM

Lisa La1, Sundar Jagannath, MD1*, Sikander Ailawadhi, MD2, Brian G.M. Durie, MD3, Cristina J. Gasparetto, MD4*, James W. Hardin, PhD5*, Hans C. Lee, MD6, Mohit Narang, MD7*, James L. Omel, MD8*, Robert M. Rifkin, MD9, Howard R. Terebelo, DO10, Kathleen Toomey, MD11*, Lynne I. Wagner, PhD12*, Mazaher Dhalla13*, Liang Liu, MS13*, Ling Yang, MS13*, Prashant Joshi, MD13* and Rafat Abonour, MD14

1Mount Sinai Hospital, New York, NY
2Mayo Clinic, Jacksonville, FL
3Cedars-Sinai Medical Center, Los Angeles, CA
4Duke University Medical Center, Durham, NC
5University of South Carolina, Columbia, SC
6The University of Texas MD Anderson Cancer Center, Houston, TX
7Maryland Oncology Hematology, US Oncology Research, Columbia, MD
8Myeloma Research Advocate/Advisor, Grand Island, NE
9Rocky Mountain Cancer Centers US Oncology Research, Denver, CO
10Providence Cancer Institute, Southfield, MI
11Steeplechase Cancer Center, Somerville, NJ
12Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC
13Bristol-Myers Squibb Company, Princeton, NJ
14Indiana University, Indianapolis, IN

Background:

Multiple myeloma (MM) is typically diagnosed in patients (pts) aged 65-74 y (SEER: Myeloma. 2019); therefore, many pts present with concomitant metabolic disorders such as diabetes (18%-22% prevalence of type 2 diabetes [T2D; BMC Cancer. 2020;20:489]). Obesity (body mass index [BMI], ≥ 30 kg/m2 ) is associated with increased prevalence of T2D (Int J Clin Pract. 2007;61:737), and both are suggested risk factors for MM (Blood. 2012;119:4845; Bone Marrow Transpl. 2014;49:1009). Results from single-center, retrospective studies have shown poorer clinical features and survival outcomes in diabetic pts with MM vs their nondiabetic counterparts (Eur J Haematol. 2012;89:320, Br J Cancer. 2014;111:628). The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of largely community-based pts with NDMM. Reported here is a descriptive analysis assessing differences in baseline (BL) characteristics, treatment patterns, and survival outcomes in diabetic vs nondiabetic pts enrolled in the Connect MM Registry.

Methods:

Pts with NDMM (N = 3011) were enrolled at 250 community, academic, and government sites. Eligible pts were aged ≥ 18 y with symptomatic MM diagnosed ≤ 2 months (mo) pre-enrollment per International Myeloma Working Group criteria (Leukemia. 2009;23:3). Diabetic pts were defined as those with a history of diabetes and also receiving antidiabetic treatment at BL; those without a history of diabetes and not receiving antidiabetic treatment at BL were defined as nondiabetic pts. Descriptive statistics were used for BL characteristics and treatment regimens. Survival outcomes (progression-free survival [PFS] and overall survival [OS]) were analyzed using Cox regression and adjusted for covariates.

Results:

Of the 2845 pts included in this analysis, 467 (16%) were diabetic, and 2378 (84%) were nondiabetic. The median age was 69 y for diabetic pts and 66 y for nondiabetic pts, with fewer Black pts (12.2% vs 19.5%) in the nondiabetic group. The proportion of men was higher in the diabetic vs the nondiabetic group (61.9% vs 56.6%). Similar percentages of pts had ECOG PS of 0-1 in both groups (53.3% vs 55.3%). Obesity was more prevalent in diabetic vs nondiabetic pts (55.9% vs 30.4%). More diabetic pts had a history of hypertension requiring treatment vs nondiabetic pts (84.2% vs 52.5%). The prevalence of chromosomal abnormalities was comparable between the groups (within the limitation that data were missing in a substantial number of pts). Among MM-defining criteria, diabetic pts had a higher incidence of hypercalcemia (11.8% vs 8.5%), anemia (50.3% vs 46.5%), and increased creatinine (23.8% vs 19%), whereas measured kidney function was similar. A lower proportion of diabetic than nondiabetic pts received stem cell transplantation (SCT; 28.9% vs 41.5%) and triplet regimens during first induction (48.2% vs 52.8%%). The use of ≥ 2 novel agents during first line (1L) was lower in diabetic than nondiabetic pts (27.8% vs 34.6%), but use of a single novel agent (63.4% vs 60%) and alkylator in 1L (20.6% vs 22.4%) was comparable. The top five 1L regimens were similar for both groups, with lenalidomide + bortezomib + dexamethasone being the most common 1L regimen, and lenalidomide the most common maintenance therapy. Diabetic pts had significantly shorter adjusted median PFS (24.4 vs 31.5 mo; hazard ratio [HR], 1.24; P = 0.001; Fig. 1A) and median OS (60 vs 72.6 mo; HR, 1.29; P = 0.001; Fig. 1B) than nondiabetic pts. In a subgroup analysis by BMI, diabetic pts had significantly shorter OS than nondiabetic pts (for BMI < 30 [50.8 vs 73.1 mo; HR, 1.51; P = 0.0001] and BMI ≥ 30 [56.4 vs 78.6 mo; HR, 1.51; P < 0.0001]).

Conclusions:

Diabetic pts with NDMM had poorer BL features and were less likely to receive SCT and triplet regimens and/or aggressive upfront treatment. Regardless of BMI, diabetic pts had shorter median OS than nondiabetic pts, suggesting that diabetes might be a stronger factor for survival than obesity. These results support a previous analysis of the Connect MM Registry that identified history of diabetes as a predictive prognostic factor for poor OS (Br J Haematol. 2019;187:602). Limitations of this analysis include limited detail on the care/management of diabetes and steroid use/dosage (which can be challenging for glycemic control). These findings highlight the need to provide better supportive care for diabetes management in MM pts to improve survival.

Disclosures: La: Celgene BMS: Consultancy. Jagannath: BMS, Janssen, Karyopharm, Legend Biotech, Sanofi, Takeda: Consultancy. Ailawadhi: Janssen: Research Funding; Takeda: Honoraria; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding; Beigene: Consultancy; GSK: Consultancy; Amgen: Research Funding; Celgene: Honoraria; Oncopeptides: Consultancy. Durie: Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Gasparetto: Adaptive Biotechnologies: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Karyopharm: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Honoraria. Hardin: Celgene Pharmaceutical Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Lee: Sanofi: Consultancy; Janssen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; Takeda: Consultancy, Research Funding; Regeneron: Research Funding; Genentech: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Research Funding. Narang: Maryland Oncology Hematology: Current Employment; Beigene: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; J&J: Consultancy, Honoraria. Omel: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rifkin: McKesson: Current equity holder in publicly-traded company, Ended employment in the past 24 months, Other: Stock ownership; Takeda, Amgen, Celgene, BMS, Mylan, Coherus BioSciences, Fresenius: Consultancy; AbbVie: Other: Investigator in AbbVie sponsored clinical trials; Takeda, Amgen, BMS (Celgene): Membership on an entity's Board of Directors or advisory committees. Terebelo: Newland Medical Associates: Current Employment; BMS: Membership on an entity's Board of Directors or advisory committees. Toomey: Celgene/BMS: Membership on an entity's Board of Directors or advisory committees. Wagner: Connect Multiple Myeloma Registry: Membership on an entity's Board of Directors or advisory committees; Celgene Inc.: Membership on an entity's Board of Directors or advisory committees. Dhalla: BMS: Current Employment, Current equity holder in publicly-traded company. Liu: TechData Inc: Consultancy. Yang: BMS: Current Employment, Current equity holder in publicly-traded company. Joshi: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company; Eisai Inc.: Ended employment in the past 24 months. Abonour: Takeda: Consultancy; Janssen: Honoraria, Research Funding; Celgene: Consultancy; BMS: Consultancy, Research Funding.

*signifies non-member of ASH