High (95%) Response Rates in Relapsed/Refractory Mantle Cell Lymphoma after R-HCVAD Alternating with R-Methotrexate/Cytarabine (R-M-A).
Authors: Romaguera Jorge Enrique , Fayad Luis E. , Wang Michael , Cabanillas Fernando , Hagemeister Fredrick , McLaughlin Peter , Rodriguez Alma , Younes Anas , Neelapu Sattva , Goy Andre H. , Beasley Virginia , Kwak Larry 
Published: April 2020

Abstract
Mantle cell lymphoma (MCL) has a poor prognosis. Relapsed/refractory patients must respond to salvage chemotherapy in order to receive potentially curative stem cell transplantation (SCT). A salvage regimen with higher rate of response will offer the patient a better chance of survival. We have previously reported the results of R-HCVAD alternating with R-M-A in frontline therapy of MCL (Blood, 104:40a, 2004, (Abstract #128).
The current trial looked at relapsed/refractory MCL patients treated also with R-HCVAD alternating with R-M-A. Since August 2001, the trial has accrued 24 out of a planned number of 41 patients of whom 21 are evaluable for response and survival. Median age was 63 years (range 45–78) and male:female ratio was 5:1. Three patients had received previous R-HCVAD alternating with R-M-A and three patients had failed an autologous stem cell transplant. Immediate therapy prior to the study for the 21 patients included R-HCVAD/SCT (1), CHOPw/wo rituximab (8 patients), cyclophosphamide, vincristine and rituximab (1), fludarabine (1), fludarabine, mitoxantrone, dexamethasone and rituximab (2), fludarabine and cyclophosphamide (1), radiotherapy (2), gemcitabine, mitoxantrone and dexamathasone (1) ifosfamide, carboplatin, etoposide and rituximab (1), Velcade (1), gemcitabine (1), and rituximab (1). The median number of prior regimens was one (range 1–6). Responses to the previous treatment included complete response (CR; 8 patients, 38%), partial response (PR; 6 patients, 29%), and no response or progression (7 patients, 33%). Results of the trial are as follows: Median number of cycles received = 4 (range 1–7), with an overall response rate (ORR) of 95% (43% CR/Cru; 52% PR). 5/5 patients who had progressed through the previous treatment responded (1CR, 4 PR), and 2/2 patients who had no change to the prior therapy responded (2 PR’s). We evaluated 12 cases whose response in our trial was classified as PR and found that in 4 of them it was the best response achieved but another 4 were referred to transplant while the tumor was still responding and in another case treatment was still ongoing. In 3 cases toxicity precluded continuation of therapy. Five (24%) of the patients were consolidated with non-myeloablative allogeneic stem cell transplantation. Sixteen were not transplanted for the following reasons: age (2 patients), lack of donor (5), Progressive disease (2), patient refusal (4), physician’s choice (1), waiting for match (1), and lost to follow up (1). Toxicity after 81 cycles included neutropenic fever (14%), grade 4 neutropenia (58%) and grade 4 thrombocytopenia (53%). The were no deaths due to toxicity. With a median follow-up of 21 months range 5–45 months), the median failure-free survival is 18 months as compared to a median FFS of 9 months response duration with the previous therapy, with no plateau in the curve. Patients who underwent stem cell transplant were censored at the time of transplant.
The high response rates achieved R-HCVAD alternating with R-M-A makes this regimen an excellent choice for induction therapy prior to stem cell transplantation.