On the 2nd April 2017, in correspondence to the British Journal of Haematology, Samer A. Srour from The University of Texas MD Anderson Cancer Center, Houston, TX, USA, and colleagues outlined results of their new, chemotherapy-free combination regimen in heavily pre-treated patients with MCL.
In an attempt to overcome resistance and improve outcomes for heavily pre-treated ibrutinib-resistant patients, the group piloted a novel, multi-agent regimen consisting of dexamethasone, rituximab, lenalidomide, and bortezomib (DR2IVE).
Five heavily pre-treated patients were treated and followed between April 2015 and May 2016. Patients were assessed clinically after each cycle and assessed for efficacy every 1–3 cycles per treating physician discretion. The patients had received a median of 3 previous lines of chemoimmunotherapy (range, 3–11), all had been previously exposed to steroids, rituximab, and ibrutinib
- Median age at relapse = 72 years (range, 60–73)
- Median number of prior chemoimmunotherapy lines = 3 (range 3–11)
- All 5 pts had prior exposure to: steroids, rituximab, and ibrutinib
- Previous exposure to bortezomib in 4/5
- Previous exposure to lenalidomide in 1/5
- Maximum of 6 cycles:
- Dexamethasone 20–40mg PO or IV on D1, 8, 15, and 22
- Rituximab 375mg/m2 IV on D1, 8, 15, and 22
- Lenalidomide 15–20 mg PO on D1–21
- Bortezomib 1.3mg/m2 SC on D1, 8, 15, and 22
- Median number of cycles received = 2 (range, 1–6)
Efficacy and toxicity
- ORR = 100% (CR n=3, PR n=2); 3 pts alive at last follow-up
- Treatment was well tolerated in 3 pts
- Infections and Grade 3–4 gastrointestinal toxicities reported in 2 pts resulting in delayed/interrupted treatment
- One patient developed Grade 4 thrombocytopenia
- Two pts died of PD after initial response
- One patient was successfully administered 6/6 planned cycles of DR2IVE and remains in remission 3 months after the last cycle
- Another patient continues to receive treatment
The authors stated that, although their experience only included a small number of patients, it indicated that their chemotherapy-free combination of lenalidomide, bortezomib, rituximab, and dexamethasone can overcome resistance in heavily treated ibrutinib-resistant MCL patients. The favorable response reported here is similar to that found in preclinical studies indicating that bortezomib resistance can be overcome with lenalidomide.
Following on from this experience, the group are planning phase I–II clinical trials with the aim of determining the feasibility and efficacy of their novel chemotherapy-free regimen prospectively and in various clinical settings.