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2288 Prognostic Value of Translocation 11;14 in Patients with Relapsed/Refractory Myeloma Receiving Anti-CD38 Therapy

Program: Oral and Poster Abstracts
Session: 905. Outcomes Research—Lymphoid Malignancies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, health outcomes research, Plasma Cell Disorders, Diseases, Lymphoid Malignancies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Ghulam Rehman Mohyuddin, MD1, Rajshekhar Chakraborty, MD2, Gregory Calip, PhD3*, Mustafa S Ascha, PhD, MS4*, Xiaoliang Wang, PhD, MPH5*, Samuel Rubinstein, MD6*, Sascha A. Tuchman, MD, MHS7, Luciano J. Megala Costa, MD, PhD8, Benjamin Haaland9*, Smith Giri, MD, MHS10, Hira S Mian, MD11, Rafael Fonseca12 and Douglas W. Sborov, MD13

1Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, Salt Lake City, UT
2Department of Medicine, Columbia University Irving Medical Center, Thornwood, NY
3Flatiron Health Inc, New York, NY
4Flatiron Health, New York, NY
5Flatiron Health Inc., New York, NY
6Division of Hematology, University of North Carolina-Chapel Hill, Chapel Hill, NC
7Department of Medicine, Division of Hematology, The University of North Carolina at Chapel Hill, Chapel Hill, NC
8University of Alabama at Birmingham Hospital, Vestavia, AL
9University of Utah, Salt Lake City
10Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
11Department of Oncology, McMaster University, Hamilton, ON, Canada
12Division of Hematology/Oncology, Mayo Clinic, Phoenix, AZ
13Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT


The translocation t(11;14) is present in ~15% of patients newly diagnosed MM and is associated with a unique clinical and pathological phenotype, despite still being classified as standard risk MM. Ex-vivo studies have also suggested that CD38 expression is decreased in patients with MM that harbors t(11;14), and hence there is a need for real-world data that compares the efficacy of anti-CD38 therapy for patients with and without t(11;14). We used clinical and cytogenetic data from a large, group of real-world patients with relapsed/refractory MM. We hypothesized that CD38 expression would be sufficient in those with t(11;14) to permit activity of anti-CD38 antibodies and that amongst patients receiving anti-CD38 therapies, outcomes would be similar in patients with t(11;14) when compared to those without the translocation.


We conducted a retrospective cohort study using the Flatiron Health electronic health record (EHR)-derived database. We evaluated data from relapsed/refractory MM patients initiating treatment including anti-CD38 therapy in their 2nd or later line of therapy between November 2015 and December 2021. Patients were also required to have documented cytogenetic testing by FISH for high-risk cytogenetic abnormalities (HRCAs) and t(11;14). Presence of t(11;14) and HRCAs defined as deletion 17p, amplification or gain 1q21, t(4;14), t(14;16) and t(14;20) was determined from FISH testing. Our primary outcomes of interest were progression-free survival (PFS) and overall survival (OS). We used the Kaplan-Meier product limit estimator to calculate survivor functions for PFS and OS and compared equality of survivor functions between groups stratified by t(11;14) and HRCA status using log-rank tests. A multivariate analysis was done adjusting for age, sex, functional status, ISS Stage, eGFR and autologous stem cell transplant receipt. Separate analysis was performed for patients with just t(11;14) and no other HRCA, as well as those without (t11;14) and no HRCA (defined as wildtype).


An overall cohort of 1,685 patients with MM initiating anti-CD38 therapy as 2nd or later treatment with a median follow up of 22.6 months was identified. Patient characteristics are listed in Table 1.

In the overall study sample, patients with and without t(11;14) had a similar median PFS, 16.6 months and 15.0 months respectively (Figure 1, p = 0.24). Median PFS was also similar when comparing patients with t(11;14) and no HRCAs (19.9 months) to wild-type patients (19.6 months) (p = 0.59). Similar associations were observed for these comparisons in OS. Median OS for patients with and without t(11;14) was 49.8 months and 31.9 months respectively (p = 0.07). In multivariable models comparing PFS in patients with t(11;14) to patients without t(11;14), we observed similar risks (HR 1.07, 95% CI 0.80-1.44, p = 0.65) after adjustment for confounders and presence of other HRCAs. When comparing PFS in patients with t(11;14) and no HRCAs to wildtype patients, no statistically significant differences were observed (HR 1.27, 95% CI 0.84-1.94, p = 0.26). In multivariable models comparing OS in patients with t(11;14) to patients without t(11;14), we observed similarly not significant risks (HR 0.82, 95% CI 0.56-1.20, p = 0.31) after adjustment for confounders and presence of other HRCAs. When comparing OS in patients with t(11;14) and no HRCAs to wildtype patients, we also observed similar risks of overall mortality (HR 0.90, 95% CI 0.50-1.61, p = 0.72).


In this large real-world study of outcomes of anti-CD38 therapy with relapsed/refractory MM, no significant difference in outcomes were observed between those who had t(11;14) compared to those who did not. This study has important implications as t(11;14) is increasingly recognized as a unique subset of MM with different biology, treatment response rates, and prognosis. As targeted therapies specific to patients with t(11;14) such as venetoclax are increasingly utilized in this patient population, it is important to recognize that anti-CD38 therapy should remain an important part of the treatment landscape for these patients, and that synergistic strategies incorporating bcl-2 inhibition and anti-CD38 targeting should be explored further in clinical trials.

Disclosures: Chakraborty: Janssen, Sanofi Pasteur, Adaptive Biotech: Consultancy; Genentech Inc.: Research Funding. Rubinstein: Janssen: Consultancy; Sanofi: Consultancy; Roche: Consultancy; EUSA: Consultancy. Tuchman: Janssen: Honoraria; Prothena: Honoraria; Shattuck Labs: Honoraria. Megala Costa: Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; AbbVie: Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria; Genentech: Research Funding. Giri: Pack Health: Research Funding; CareVive: Honoraria, Research Funding; OncLive: Honoraria. Mian: Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Fonseca: Adaptive Biotechnologies: Divested equity in a private or publicly-traded company in the past 24 months; Adaptive Biotechnologies, Caris Life Sciences, OncoMyx and OncoTracker: Other: Scientific Advisory Board; AbbVie, Amgen, Bayer, BMS/Celgene, GSK, H3 Therapeutics, Janssen, Juno, Karyopharm, Kite, Merck, Novartis, Oncopeptides, OncoTracker, Pfizer, Pharmacyclics, Regeneron, Sanofi, Takeda: Consultancy; Adaptive Biotechnologies, Caris Life Sciences, Oncomyx and OncoTracker: Membership on an entity's Board of Directors or advisory committees; Amgen, BMS, Celgene, Takeda, Bayer, Janssen, Novartis, Pharmacyclics, Sanofi, Merck, Juno, Kite, Aduro, OncoTracker, GSK, AbbVie, Pfizer, Karyopharm.: Consultancy; Genentech, Pfizer, Sanofi: Honoraria, Research Funding; FIH prognostication in myeloma: Patents & Royalties. Sborov: Abbvie: Consultancy; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bioline: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH