From the publishers of JADPRO

Multiple Myeloma Resource Center


Early Relapsed Multiple Myeloma With Translocation (11;14)

Last Updated: Tuesday, July 11, 2023


A 62-year-old black male with IgG kappa multiple myeloma with t(11;14) was initially diagnosed in 2019. His treatment history includes lenalidomide, bortezomib, and dexamethasone induction x4 cycles followed by an autologous stem cell transplant (ASCT), resulting in a very good partial remission. He did well on lenalidomide maintenance for about 2 years before he started with a biochemical progression with a slow rise in his IgG paraprotein and free kappa light chain (FKLC), with subsequent development of new lytic disease on PET. His marrow demonstrates 40% plasma cells, flow positive, and fluorescence in situ hybridization (FISH) noting t(11;14) in 42 out of 50 cells. There are no cytogenetic abnormalities. Other comorbidities include hypertension, grade 1 peripheral neuropathy to both feet, and type 2 diabetes mellitus, well controlled. 


After discussing all the available options in the early relapse setting with the patient, he decided to participate in M15-654, a phase 1/2 clinical trial evaluating venetoclax, daratumumab, and dexamethasone (VenDd) with or without bortezomib (VenDVd). The patient was randomized to the VenDd arm, with venetoclax at a dose of 800 mg. He was already on an antiviral with valacyclovir, so Pneumocystis jirovecii pneumonia prophylaxis was added, along with zoledronic acid. On day 1 of cycle 1, his M protein was 1.92 g/dL, and his FKLC was 44.4 mg/L with stable counts and renal function. He did well, with a confirmed complete response after 2 cycles.  

The patient developed recurrent upper respiratory infections, and his IgG quantitative level dropped to 345 mg/dL, so monthly intravenous immunoglobulin (IVIG) was initiated. Hypogammaglobulinemia is common in patients with myeloma who are on daratumumab, as the anti-CD38 monoclonal antibody can cause plasma cell death and also targets normal lymphocytes, resulting in an impaired polyclonal response. Monthly IVIG may help in subgroups of myeloma patients, and it is recommended to keep immunoglobulin G levels greater than 600-700 mg/dL depending on your institution’s guidelines. 1-3 In addition, his dose of venetoclax was reduced to 600 mg due to the recurrent infections as well as fatigue and a slight increase in his peripheral neuropathy. The follow-up bone marrow biopsy results showed <5% plasma cells, flow cytometry negative for myeloma cells, FISH negative, and normal chromosome analysis. The patient continues in stringent complete response and is tolerating his treatment well. 


Translocation (11;14) occurs in about 16% to 24% of patients with myeloma and is considered standard risk,4-9 with black patients having a higher incidence.10,11 Myeloma cell lines with t(11;14) have a dependence on Bcl-2 12,13 for survival, making a Bcl-2 targeted therapy agent a possibility. Venetoclax is a small-molecule oral Bcl-2 inhibitor14-16 that has been studied as monotherapy as well as in combination with dexamethasone17and now is being studied in many combinations.  

The M15-654 phase l/2 study of venetoclax plus daratumumab and dexamethasone, with or without bortezomib, in patients with relapsed or refractory multiple myeloma with and without t(11;14), evaluates safety, tolerability, and efficacy in three distinct parts.18 Our patient went on to receive part 1, VenDd with venetoclax 800 mg. The overall response rate was 96% with VenDd, with the 18-month progression-free survival rate at >90%. The most common adverse events were mild gastrointestinal events and fatigue, as reported with single-agent venetoclax.17 Increased upper respiratory tract infections were experienced, similar to what has been demonstrated with daratumumab and hypogammaglobulinemia.19 There was no overall increase in serious side effects. 

According to the NCCN Guidelines,20 there are many treatment options to consider and discuss with patients experiencing early relapse. When discussing new treatment modalities, it is important to consider prior therapies along with any comorbidities or side effects they may have experienced. This case is an example of a shared decision-making opportunity, and a reminder to review all available treatment options, including a clinical trial. As advanced practitioners, we are in the ideal role to be sure our patients feel educated, informed, and part of the decision-making process throughout their cancer journey. 



  1. Karlsson J, Andréasson B, Kondori N, et al. Comparative study of immune status to infectious agents in elderly patients with multiple myeloma, Waldenstrom's macroglobulinemia, and monoclonal gammopathy of undetermined significance. Clin Vaccine Immunol. 2011;18(6):969-977. doi:10.1128/CVI.00021-11 
  2. Lancman G, Lozada K, Athar N, et al. Efficacy of intravenous immunoglobulin for preventing infections in patients with multiple myeloma. Clin Lymphoma Myeloma Leuk. 2021;21(5):e470-e476. doi:10.1016/j.clml.2020.12.026 
  3. Miceli TS, Gonsalves WI, Buadi FK. Supportive care in multiple myeloma: Current practices and advances. Cancer Treat Res Commun. 2021;29:100476. doi:10.1016/j.ctarc.2021.100476 
  4. Kaufman GP, Gertz MA, Dispenzieri A, et al. Impact of cytogenetic classification on outcomes following early high-dose therapy in multiple myeloma. Leukemia. 2016;30(3):633-639. doi:10.1038/leu.2015.287 
  5. Avet-Loiseau H, Attal M, Moreau P, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood. 2007;109(8):3489-3495. doi:10.1182/blood-2006-08-040410 
  6. Avet-Loiseau H, Facon T, Grosbois B, et al. Oncogenesis of multiple myeloma: 14q32 and 13q chromosomal abnormalities are not randomly distributed, but correlate with natural history, immunological features, and clinical presentation. Blood. 2002;99(6):2185-2191. doi:10.1182/blood.v99.6.2185 
  7. Fonseca R, Blood EA, Oken MM, et al. Myeloma and the t(11;14)(q13;q32); evidence for a biologically defined unique subset of patients. Blood. 2002;99(10):3735-3741. doi:10.1182/blood.v99.10.3735 
  8. Gasparetto C, Jagannath S, Rifkin RM, et al. Effect of t (11;14) Abnormality on outcomes of patients with newly diagnosed multiple myeloma in the Connect MM Registry. Clin Lymphoma Myeloma Leuk. 2022;22(3):149-157. doi:10.1016/j.clml.2021.08.007 
  9. Bal S, Kumar SK, Fonseca R, et al. Multiple myeloma with t(11;14): unique biology and evolving landscape. Am J Cancer Res. 2022;12(7):2950-2965. Published 2022 Jul 15. 
  10. Baughn LB, Pearce K, Larson D, et al. Differences in genomic abnormalities among African individuals with monoclonal gammopathies using calculated ancestry. Blood Cancer J. 2018;8(10):96. Published 2018 Oct 10. doi:10.1038/s41408-018-0132-1 
  11. Diamantidis MD, Papadaki S, Hatjiharissi E. Exploring the current molecular landscape and management of multiple myeloma patients with the t(11;14) translocation. Front Oncol. 2022;12:934008. Published 2022 Aug 2. doi:10.3389/fonc.2022.934008 
  12. Bodet L, Gomez-Bougie P, Touzeau C, et al. ABT-737 is highly effective against molecular subgroups of multiple myeloma. Blood. 2011;118(14):3901-3910. doi:10.1182/blood-2010-11-317438  
  13. Touzeau C, Ryan J, Guerriero J, et al. BH3 profiling identifies heterogeneous dependency on Bcl-2 family members in multiple myeloma and predicts sensitivity to BH3 mimetics. Leukemia. 2016;30(3):761-764. doi:10.1038/leu.2015.184 
  14. Gupta VA, Ackley J, Kaufman JL, Boise LH. BCL2 Family inhibitors in the biology and treatment of multiple myeloma. Blood Lymphat Cancer. 2021;11:11-24. Published 2021 Mar 12. doi:10.2147/BLCTT.S245191 
  15. Kaufman JL, Gasparetto C, Schjesvold FH, et al. Targeting BCL-2 with venetoclax and dexamethasone in patients with relapsed/refractory t(11;14) multiple myeloma. Am J Hematol. 2021;96(4):418-427. doi:10.1002/ajh.26083 
  16. Touzeau C, Maciag P, Amiot M, Moreau P. Targeting Bcl-2 for the treatment of multiple myeloma. Leukemia. 2018;32(9):1899-1907. doi:10.1038/s41375-018-0223-9 
  17. Kumar S, Kaufman JL, Gasparetto C, et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood. 2017;130(22):2401-2409. doi:10.1182/blood-2017-06-788786 
  18. Bahlis NJ, Baz R, Harrison SJ, et al. Phase I study of venetoclax plus daratumumab and dexamethasone, with or without bortezomib, in patients with relapsed or refractory multiple myeloma with and without t(11;14). J Clin Oncol. 2021;39(32):3602-3612. doi:10.1200/JCO.21.00443 
  19. Ludwig H, Delforge M, Facon T, et al. Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network. Leukemia. 2018;32(7):1542-1560. doi:10.1038/s41375-018-0040-1 
  20. NCCN Guidelines. Multiple Myeloma (version 3.2023) Last accessed June 28, 2023. 


Test your knowledge of multiple myeloma with t(11;14)

Last Updated: Tuesday, July 11, 2023
News & Literature Highlights