Venetoclax-based treatment combinations in relapsed/refractory multiple myeloma: practice patterns and impact of secondary cytogenetic abnormalities on outcomes - Scorecard - MDSpire

Venetoclax-based treatment combinations in relapsed/refractory multiple myeloma: practice patterns and impact of secondary cytogenetic abnormalities on outcomes

  • By

  • Abiola Bolarinwa

  • Madhu Nagaraj

  • Saurabh Zanwar

  • Nadine Abdallah

  • P. Leif Bergsagel

  • Moritz Binder

  • Francis Buadi

  • Saurabh Chhabra

  • Joselle Cook

  • David Dingli

  • Angela Dispenzieri

  • Morie A. Gertz

  • Wilson Gonsalves

  • Suzanne Hayman

  • Prashant Kapoor

  • Taxiarchis Kourelis

  • Nelson Leung

  • Yi Lin

  • Eli Muchtar

  • Ricardo Parrondo

  • Vivek Roy

  • Taimur Sher

  • Mustaqeem Siddiqui

  • Rahma Warsame

  • Amie Fonder

  • Miriam Hobbs

  • Yi Lisa Hwa

  • Michelle Rogers

  • Udit Yadav

  • J. Erin Wiedmeier-Nutor

  • Linda B. Baughn

  • S. Vincent Rajkumar

  • Rafael Fonseca

  • Sikander Ailawadhi

  • Shaji Kumar

  • April 4, 2025

  • 0 min

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Clinical Scorecard: Combination Therapies Involving Venetoclax for Relapsed/Refractory Multiple Myeloma: Treatment Trends and the Influence of Secondary Cytogenetic Abnormalities on Patient Outcomes

At a Glance

CategoryDetail
ConditionRelapsed/Refractory Multiple Myeloma (RRMM)
Key MechanismsVenetoclax inhibits BCL-2, an anti-apoptotic protein overexpressed in ~20% of MM patients, especially those with t(11;14), promoting apoptosis in myeloma cells reliant on BCL-2 for survival.
Target PopulationPatients with RRMM, particularly those with t(11;14) cytogenetic abnormality or high BCL-2 expression.
Care SettingSpecialized oncology centers with access to venetoclax-based combination therapies and cytogenetic testing.

Key Highlights

  • Venetoclax-based combinations show high response rates (40-50% in t(11;14) patients; up to 80% in combination regimens) and improved progression-free survival in RRMM.
  • Efficacy is pronounced in patients with t(11;14) due to induced BCL-2 dependency; lower efficacy observed in non-t(11;14) patients despite high BCL-2 expression.
  • Concerns remain regarding overall survival and infection risks with venetoclax combinations, as highlighted by the BELLINI and CANOVA trials.

Guideline-Based Recommendations

Diagnosis

  • Perform fluorescence in-situ hybridization (FISH) to detect t(11;14) and other cytogenetic abnormalities.
  • Assess BCL-2 expression by immunohistochemistry in select patients without t(11;14).
  • Define refractory status including triple-class and penta-drug refractoriness prior to therapy initiation.

Management

  • Consider venetoclax-based combination therapies (e.g., Venetoclax with carfilzomib and dexamethasone or daratumumab-based regimens) for RRMM patients, especially those with t(11;14).
  • Monitor for infectious complications due to increased risk observed in venetoclax-treated patients.
  • Use venetoclax cautiously in heavily pretreated patients and consider secondary cytogenetic abnormalities when selecting therapy.

Monitoring & Follow-up

  • Regularly assess treatment response using International Myeloma Working Group (IMWG) criteria.
  • Monitor progression-free survival, overall survival, and adverse events including infections.
  • Evaluate cytogenetic status periodically to detect secondary abnormalities that may influence outcomes.

Risks

  • Increased risk of infections potentially impacting overall survival.
  • Uncertain benefit in non-t(11;14) patients despite high BCL-2 expression.
  • Potential adverse effects leading to treatment discontinuation.

Patient & Prescribing Data

232 patients with RRMM treated with venetoclax-based combinations at Mayo Clinic between 2015 and 2023.

Venetoclax combinations yielded high overall response rates and progression-free survival, particularly in t(11;14) patients; however, survival benefits may be offset by infection risks and variable efficacy in non-t(11;14) cohorts.

Clinical Best Practices

  • Select patients for venetoclax therapy based on cytogenetic profiling, prioritizing those with t(11;14).
  • Combine venetoclax with proteasome inhibitors, immunomodulatory drugs, or monoclonal antibodies to enhance efficacy.
  • Implement vigilant infection surveillance and prophylaxis during venetoclax treatment.
  • Use standardized response criteria (IMWG) and robust statistical methods to evaluate treatment outcomes.
  • Consider secondary cytogenetic abnormalities when interpreting venetoclax efficacy and planning therapy.

References

Original Source(s)

Venetoclax-based treatment combinations in relapsed/refractory multiple myeloma: practice patterns and impact of secondary cytogenetic abnormalities on outcomes

  • by Abiola Bolarinwa, Madhu Nagaraj, Saurabh Zanwar, Nadine Abdallah, P. Leif Bergsagel, Moritz Binder, Francis Buadi, Saurabh Chhabra, Joselle Cook, David Dingli, Angela Dispenzieri, Morie A. Gertz, Wilson Gonsalves, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Nelson Leung, Yi Lin, Eli Muchtar, Ricardo Parrondo, Vivek Roy, Taimur Sher, Mustaqeem Siddiqui, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Michelle Rogers, Udit Yadav, J. Erin Wiedmeier-Nutor, Linda B. Baughn, S. Vincent Rajkumar, Rafael Fonseca, Sikander Ailawadhi, Shaji Kumar

  • April 4, 2025

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