Sustained Graft-Versus-Lymphoma Effect among Patients (pts) with Mantle Cell Lymphoma (MCL) Given Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation (HCT).
Authors: Sorror Mohamed L. , Storer Barry , Sandmaier Brenda M. , Maris Michael , Chauncey Thomas , Maziarz Richard T. , Pulsipher Michael , Shizuru Judith , Niederwieser Dietger , Agura Edward , Wade James C. , Langston Amelia A , Storb Rainer F. , Maloney David G. 
Published: April 2020

We previously reported 2-year overall survival (OS) of 65% among 33 pts with MCL given nonmyeloablative HCT (Blood2004; 104: 3535). Here, we update our results on the initial 33 pts with median follow up of 63 months and report on 20 additional pts with emphasis on:

long-term disease control and resolution of chronic GVHD.

Pts were conditioned with 2Gy TBI with or without fludarabine (90 mg/m2). Median age for all pts was 56 (range 33–75) years and median number of prior regimens was 4. Forty percent of pts had failed high-dose autologous HCT and an additional 11% had planned autologous HCT before allograft (4 pts had refractory disease and 2 were in PR). Comorbidity scores of ≥3 were found among 40% of pts. Forty percent of pts were not in CR/PR at HCT and 26% and 21% had marrow infiltration and lymph node size ≥5 cm, respectively. Donors were related (n=28) or unrelated (n=25). After HCT, incidences of grades II, III, and IV acute GVHD were 25%, 13%, and 9% respectively, and chronic extensive GVHD was 53%. Complete (CR) and partial remissions (PR) were seen in 71% and 3% of pts with measurable disease at HCT, respectively. Estimated 5-year rates of non-relapse mortality (NRM), progression/relapse, OS, and progression-free survival (PFS) were 27%, 22%, 58%, and 52%, respectively (Table 1). Among 19 pts in CR at HCT, 11 are alive and in CR, 7 died in CR, and one relapsed (now in CR after Rituximab and donor lymphocyte infusion). Among 13 in PR at HCT, 10 achieved CR and are alive, one died in PR, and 2 died from relapse. Among 21 pts with refractory/relapsed disease at HCT, 12 achieved CR and are alive, 2 have stable disease and are alive, and 7 relapsed (2 are alive in CR and PR after further treatment). At 5-years, 44% and 14% were alive without or with chronic GVHD requiring immunosuppression (Figure); and median duration of treatment for chronic GVHD was 33 months. Outcomes were comparable among related and unrelated recipients. Relapse rates were 47% vs. 14% among pts with vs. without LN size of ≥5 cm (p=0.02) and NRM was 41% vs.17% (p=0.05) among pts with HCT-CI scores of ≥3 vs. 0–2, respectively. Nonmyeloablative HCT is a potentially curative therapeutic modality for pts with advanced MCL, including patients who were chemotherapy-refractory, with a median PFS beyond 5 years. Sustained remissions and continuing resolution of chronic GVHD were observed with extended follow up. Pts with bulky LN might benefit from further debulking strategies before HCT.

Table: Outcomes by donor type

Donor Related (n = 28) Unrelated (n = 25) % % Grades III–IV non-hematological toxicities 39/18 38/26 Acute GVHD, grades II/ III/ IV 22/14/7 28/12/12 Chronic GVHD 50 55 CR 73 67 5-year NRM 26 28 5-year Progression/relapse 22 21 5-year PFS 53 51 5-year OS 59 56 5-year Pts alive with chronic GVHD requiring immunosuppression 14 7 Figure Figure