Venetoclax in Combination With Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Harboring t(11,14)(q13;q32)

Two Case Reports and a Review of the Literature

Khadega A. Abuelgasim; Noha Alherz; Ayman Alhejazi; Moussab Damlaj

Disclosures

J Med Case Reports. 2020;14(54) 

In This Article

Discussion and Conclusions

Different subpopulations of patients with MM have different outcomes driven by well-characterized genetic abnormalities that occur at various time points of the disease course.[12,13] Specific cytogenetic abnormalities in MM affect clinical presentation, prognosis, and more recently management strategies. The t(11;14) is a common primary cytogenetic abnormality in MM. Patients with MM who have t(11;14) tend to present with more bone disease and are considered to be at standard risk with a median overall survival of 7–10 years.[14,15] Both of our patients presented with bony lesions; although one is still alive more than 6 years after diagnosis, the other died within 2 years of diagnosis.

Among the known secondary cytogenetic abnormalities that are acquired during the course of disease, usually with disease progression, are t(4;14), t(14;20), t(14;16), Myc translocation, 1q amplification, 17p deletion, and 1p deletion.[16] The result of patient 1's diagnostic FISH was negative for the known myeloma-related cytogenetic abnormalities; he subsequently acquired t(11;14)(q13;q32) 5 years into his disease course, which had been unreported in the MM literature to date. In the era of targeted therapy, it is essential to repeat the MM FISH panel with each disease progression to allow precision therapy.

Patients with MM who have t(11;14)(q13;q32) are known to have an excellent response to lenalidomide-based therapy.[17] Our patient 1 received multiple lenalidomide-based regimens and is still alive more than 6 years after diagnosis, whereas our patient 2 could not receive lenalidomide due to extreme allergy, which might have contributed to his worse outcome and shorter survival.

Venetoclax combinations, including VenKd, showed promising preliminary results in patients with RRMM in phase Ib and phase II studies; however, all of these studies had short follow-up.[9–11] Venetoclax in patients with MM harboring t(11,14)(q13;q32) is considered the first example of personalized/precision therapy in the field of MM; however, more clinical studies with longer follow-up are needed before its adoption in clinical practice. Both of our patients had disease that failed to respond to multiple regimens, including those containing carfilzomib and dexamethasone. In both patients, VenKD resulted in a rapid initial response; however, one patient's disease progressed after 6 months, whereas the other's progressed after only 2 months.

MM remains a challenging hematological malignancy that we fail to cure despite advances in personalized/precision medicine. In the era of targeted therapy, it is essential to repeat the MM FISH panel with each disease progression to allow for precision therapy. The use of novel MM therapeutic combinations is better done within a clinical trial.

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