Outcomes of venetoclax-based therapy in patients with t(11;14) light chain amyloidosis after failure of daratumumab-based therapy

Abstract

Background

Daratumumab’s incorporation in the upfront treatment of light chain (AL) amyloidosis has led to daratumumab (dara) refractoriness early in disease course. Patients who experience relapse or have suboptimal response to dara-based-therapy, have limited options.

Objective

This study aimed to evaluate the outcomes of venetoclax-based therapy in t(11;14) positive AL patients who previously failed dara.

Methods

Thirty-one patients with AL were included in this bi-institutional retrospective analysis.

Results

Dara failure was due to inadequate response in 20 (65%) patients, haematologic relapse in 7 (22%), and both haematologic plus organ relapse in 4 (13%). Overall haematologic response rate to venetoclax-based therapy was 97%, with ≥ VGPR being 91%. Of the 19 evaluable patients with cardiac involvement, 14 (74%) achieved organ response. Of the 13 evaluable patients with renal involvement, 6 (46%) achieved organ response. With a median follow-up of 22 months, median time-to-next-treatment (TTNT) and overall survival (OS) were not reached. The 12- and 24-month TTNT rates were 74% and 56%, respectively. At data-cut-off, four patients had died, all from AL-related organ complications. The 12- and 24-month OS rates were 89% and 85%, respectively. Grade ≥3 adverse events occurred in 26% of patients, with 6% due to infections.

Conclusion

These findings are encouraging for the use of venetoclax as salvage therapy post-dara failure.

Keywords:

• Daratumumab
• light chain amyloidosis
• treatment failure
• venetoclax

Acknowledgments

We would like to thank all the members of the myeloma care teams, including physicians, nurses, pharmacists, and coordinators, at the contributing institutions.

Authors’ contributions

Conception and design: DD, MH, JK, RC. Provision of study materials or patients: All authors. Collection and assembly of data: All authors. Data analysis and interpretation: DD, MH, JK, RC. Manuscript writing: All authors. Final approval of manuscript: All authors.

Disclosure statement

Faiz Anwer: Research Funding and Consultancy for BMS, Janssen, Allogene Therapeutics. Jack Khouri: Consultancy for Janssen. Jason Valent: Research Funding from Alexion, AstraZeneca Rare Disease. Shahzad Raza: Advisory Board for Kite Pharma, Pfizer and Prothena biosciences. Louis Williams: Consulting for BMS, Janssen, Abbvie. Suzanne Lentzsch: Janssen (consulting/advisory), GlaxoSmithKline (consulting/ advisory), Pfizer (consulting/advisory), Bristol-Myers-Squibb (consulting/advisory), Adaptive Biotech-nologies (consulting/advisory), Sanofi (consulting/advisory; research funding), Karyopharm Therapeutics (consulting/advisory), Regeneron (consulting/advisory; travel, accommodations, expenses), Alexion Pharmaceuticals (consulting/advisory), Bluebird Bio (consulting/advisory, immediate family), Crispr Tx (consulting/advisory, immediate family), Incyte (consulting/advisory, immediate family), PeerView (Speakers’ Bureau), Clinical Care Options (Speakers’ Bureau), BioAscent (Speakers’ Bureau), RedMedEd.com (Speakers’ Bureau), Patent 11-1F4 mAb for use in AL Amyloidosis (patents, royalties, other intellectual property), Poseida Therapeutics (stock/other ownership, immediate family), Dianthus Therapeutics (stock/other ownership, immediate family). Divaya Bhutani: Sanofi (consulting/advisory; research funding). Rajshekhar Chakraborty: Consulting/Advisory Board-Janssen, Sanofi, and Adaptive Biotech; Research Funding: AbbVie and Genentech. The rest of the authors have no financial or non-financial potential conflicts of interest.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.