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Clinical Trial
. 2024 Apr 9;8(7):1612-1620.
doi: 10.1182/bloodadvances.2023011369.

A phase 1-2 trial of DA-EPOCH-R plus ixazomib for MYC-aberrant lymphoid malignancies: the DACIPHOR regimen

Reem Karmali  1   2 , Carlos Galvez  1 , Mehdi Hamadani  3 , Leo Gordon  1   2 , Jane Winter  1   2 , Shuo Ma  1   2 , Valerie Nelson  1   2 , Timothy S Fenske  3 , Nirav N Shah  3 , Deepa Jagadeesh  4 , Andreas Klein  5 , Irene Helenowski  6 , Ruohui Chen  6 , Xinlei Mi  6 , Adam Petrich  1   2   7 , Andrew M Evens  8 , Barbara Pro  1   2
Affiliations
Clinical Trial

A phase 1-2 trial of DA-EPOCH-R plus ixazomib for MYC-aberrant lymphoid malignancies: the DACIPHOR regimen

Reem Karmali et al. Blood Adv. .

Abstract

MYC-aberrant non-Hodgkin lymphoma (NHL) is associated with poor outcomes with conventional chemotherapy. Ixazomib is an orally bioavailable proteasome inhibitor that targets drivers of MYC expression and has demonstrated preclinical activity in aggressive MYC-aberrant NHL. We conducted a phase 1/2 study evaluating the safety and efficacy of DA-EPOCH-R with adjunctive ixazomib in aggressive MYC-aberrant NHL. For induction, patients received 6 cycles of DA-EPOCH-R with ixazomib administered twice per 21-day cycle; responders continued weekly ixazomib maintenance for up to 1 year. Primary objectives were to determine the maximum tolerated dose in phase 1 and efficacy of DA-EPOCH-R with ixazomib as measured by 12-month progression-free survival (PFS) rate in phase 2. Thirty-six patients were evaluable for response. Median age was 63 years (range, 31-77) and 44% had double-hit lymphoma (DHL)/triple-hit lymphoma (THL). In phase 1, 3 mg of ixazomib was established as recommended phase 2 dose. Twenty-nine (76.3%) patients completed 6 cycles of DA-EPOCH-R and 25 (65.8%) underwent dose escalations. The ORR after induction was 97% (95% confidence interval, 81-100) with a CR rate of 69%. At median follow-up of 18.8 months, the 12-month PFS and overall survival (OS) rates were 78% and 86%, respectively. For DHL/THL vs dual expressor lymphomas (DEL), 12-month PFS rates were 53% vs 95% and 12-month OS rates were 65% vs 100%, respectively. Grade ≥3 toxicities were predominantly hematologic. Twenty-seven (75%) of patients experienced neuropathy, nearly all low-grade. DA-EPOCH-R induction with adjunctive ixazomib is feasible and appears effective in patients with DEL. This trial was registered at www.clinicaltrials.gov as #NCT02481310.

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Conflict of interest statement

Conflict-of-interest disclosure: R.K. reports serving on advisory boards of BeiGene, Genentech/Roche, AstraZeneca, Miltenyi, Lilly, Calithera, Kite/Gilead, and Bristol Myers Squibb; serving on speakers' bureaus of BeiGene, AstraZeneca, and MorphoSys; and reports institutional research support from BeiGene, Takeda, Calithera, Kite/Gilead, and Bristol Myers Squibb. B.P. received honoraria from Seattle Genetics and Takeda, and is a consultant at BioSecura. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
PFS and OS Kaplan-Meier curves for DHL/THL, DEL, and MYC.
See this image and copyright information in PMC

References

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