VENETOCLAX FOR THE TREATMENT OF MULTIPLE MYELOMA: OUTCOMES OUTSIDE OF CLINICAL TRIALS
Author(s): ,
M Hasib Sidiqi
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Abdullah S Al Saleh
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Shaji Kumar
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Gertz Morie
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Angela Dispenzieri
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Francis Buadi
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Martha Lacy
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Nelson Leung
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States;Division of Nephrology,Mayo Clinic Rochester,Rochester,United States
,
Eli Muchtar
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Robert Kyle
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Ronald Go
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Miriam Hobbs
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Wilson Gonsalves
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Taxiarchis Kourelis
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Rahma Warsame
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
David Dingli
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
John Lust
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Suzanne Hayman
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
,
Vincent Rajkumar
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
Prashant Kapoor
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester,United States
EHA Library. Sidiqi M. Jun 15, 2019; 267039; PS1422
M Hasib Sidiqi
M Hasib Sidiqi
Contributions
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Abstract

Abstract: PS1422

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Venetoclax is a B cell lymphoma 2 (BCL-2) inhibitor that has shown activity as a single agent and in combination with other therapies in patients with multiple myeloma, particularly those harboring t(11;14) associated with high BCL-2 expression. Although early clinical trial data is encouraging (monotherapy response rate of 21% and 40% amongst t(11;14) and a response rate of 97% when used in combination with bortezomib and dexamethasone), data on outcomes in patients treated outside of clinical trial setting are sparse.

Aims
We aimed to identify the efficacy of venetoclax in patients with multiple myeloma treated outside clinical trial.

Methods
We conducted a retrospective review of all patients with multiple myeloma treated with venetoclax between December 2016 and February of 2019 at the Mayo Clinic outside of a clinical trial setting.

Results
A total of 29 patients that were treated with venetoclax for relapsed or refractory multiple myeloma were identified. Characteristics of the cohort are reported in Table 1. Two thirds of the cohort had t(11;14) detected on cytogenetic studies and 48% (n=14) had presence of high risk abnormalities. Median number of prior therapies was 6 (range 1-15) and 21% (n=6) of patients had received ≥10 prior lines of therapy. Eighty three percent (n=24) of patients had received prior autologous transplant and 76% (n=22) were penta refractory or exposed. Median time from diagnosis of myeloma to initiation of venetoclax therapy was 5.3 years (range 0.8-23.6 years).

Venetoclax used as monotherapy or a doublet in combination with dexamethasone in 59% (n=17) of patients and a triplet or quadruplet in 41% (n=12) given at 800mg (55%) or 400mg (35%) daily. Triplet and quadruplet regimens combined venetoclax with a variety of proteasome inhibitors or daratumumab. One patient had a quadruplet of venetoclax, carfilzomib, pomalidomide and dexamethasone. 93% (n=27) patients were refractory to at least on proteasome inhibitor and immunomodulatory drug.  Dose titration and escalation was used in 31% (n=9) of patients. None of the patients experienced tumor lysis syndrome. At last follow-up 55% (n=16) of patients remain on venetoclax therapy. Overall response rate in the 24 patients evaluable for response was 46% (21% CR, 8% VGPR, 17% PR). Patients with t(11;14) had a numerically higher response rate than those without (50% vs 33%, p=0.64). Patients with high risk cytogenetic abnormalities were less likely to respond (ORR 69% for standard risk vs 18% for high risk, p=0.019). Median time to response was 2.6 months (range 1.1-6.9 months). Median duration of response was 5.2 months (range 2.2-12.9 months). After a median follow-up time of 7.2 months for the cohort, the median PFS and OS are 5.8 and 14.6 months, respectively, Figure 1A/B. High risk cytogenetic abnormalities were associated with a shorter PFS (median PFS 3 months vs 14 months for standard risk, p=0.002). The outcomes with venetoclax monotherapy and combination therapies are reported separately in the Table.

Conclusion
Venetoclax is an effective oral agent in relapsed and/or refractory myeloma and can produce deep and durable responses in heavily pretreated patients. Further studies are needed to elucidate its role earlier in the disease and its effectiveness in combination with other anti-myeloma therapies.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): BCL2, Myeloma, Targeted therapy

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