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4651 Durability Results of Non-Myeloablative (NMA) Allogeneic Stem Cell Transplantation (alloSCT) for Relapsed Follicular Lymphoma: 17- Year Experience

Program: Oral and Poster Abstracts
Session: 732. Clinical Allogeneic Transplantation: Results: Poster III
Hematology Disease Topics & Pathways:
Biological, Adult, Follicular Lymphoma, Diseases, Therapies, Non-Hodgkin Lymphoma, Study Population, Lymphoid Malignancies, transplantation, stem cells
Monday, December 3, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Issa F. Khouri1, Denái R. Milton2*, Celina Ledesma3*, William D Erwin, MS4*, Elias J. Jabbour, MD5, Gheath Alatrash, DO, PhD6, Paolo Anderlini, MD3, Qaiser Bashir, MBBS3, Stefan O. Ciurea3, Jin S Im, MD, PhD7, David Marin, MD7, Rohtesh S. Mehta, MD, MPH, MS3, Jeffrey J. Molldrem, MD8, Amanda L. Olson, MD9, Betul Oran, MD, MS10, Uday Popat, MD3, Muzaffar H. Qazilbash, MD 3, Gabriela Rondon, MD9*, Richard E Champlin, MD3, L. Jeffrey Medeiros, MD11 and Alison Gulbis12*

1Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX
2Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
3Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
4Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX
5Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
6Department of Stem Cell Transplantation and Cellular Therapy, M.D. Anderson Cancer Center, Houston, TX
7The Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
8Stem Cell Transplantation & Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
9Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
10Stem Cell Transplantation and Cellular Therapy, The University of Texas, MD Anderson Cancer Center, Houston, TX
11Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
12Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose: We have previously reported the outcomes of NMA alloSCT in 47 patients with relapsed/chemosensitive follicular lymphoma (FL) who received a matched sibling donor (MSD) after FCR conditioning (Khouri, Blood 2008;111:5530). In subsequent trials, eligibility was expanded to include transplants from matched unrelated donors (MUDs) using a 90yttrium ibritumomab tiuxetan (90YIT)-based regimen (Khouri, Blood 2012 ;119:6373) or, more recently, BFR (bendamustine, fludarabine, rituximab; Khouri, Blood 20014;124:2306) conditioning. Herein we report on long-term outcomes in 98 FL patients treated on these 3 consecutive trials between 1999-2017. Methods: The BFR regimen (N=20) consisted of bendamustine 130 mg/m2 IV daily on days -5 to - 3 prior to transplantation, thus substituting for the cyclophosphamide in the FCR regimen (N=47) . The dose and schedule of fludarabine (30 mg/m2 IV daily x3) and rituximab (375 mg/m2 IV on day –13 and 1000 mg/m2 on days -6, +1, and +8) were similar in both regimens. 90YIT-regimens (N=31) : A diagnostic dose of 111In-ibritumomab was administered on day-14, followed by a fixed dose of 0.4 mCi/kg 90YIT on day -7; FC or BF chemo was then administered at the same dose and schedule (days -5 to -3) as described above. Tacrolimus and methotrexate was used for GVHD prophylaxis. In addition, thymoglobulin of 1 mg/kg was given on days -2, -1 in patients receiving a MUD transplant. Results: Median age was 53 years (range, 29-71) and 24 patients (24%) were >60 years. Twenty-eight patients (29%) had a HCT-CI of ≥ 3. The median prior number of treatments was 3 (range, 2-9); 51 patients (52%) had rituximab-chemo induction at diagnosis. Seventy-one patients (72%) relapsed within 2 years of their induction treatment and median duration of last remission prior to alloSCT was < 1 year in 61% of patients. At transplant, 82 patients (84%) had chemosensitive disease (46% CR, 38% PR); 16% had refractory disease; 22% were PET+; and 20% had elevated serum LDH. Seventy patients (71%) had a transplant from a MSD and 28 (29%) from MUDs; 15 (15%) transplants had female-to-male donors, and 42 (43%) were ABO-mismatched. In addition, CMV was reactive in 80% of patients/ and or donors. Most patients (94%) had alloSCT from peripheral blood. Median number of CD34-positive cells infused was 4.9 x 106/kg. A significant difference in ANC recovery between the 3 conditioning regimens was observed. Neutrophil counts recovered to > 0.5 x 109/L a median of 0 days (range 0-16) for the BFR groups vs. 10 days (range, 0-17) and 11 days (range, 5-17) for the FCR and 90YIT-regimen groups, respectively (p<0.0001). This difference was consistent for each transplant type. With a median follow-up time for all patients of 98 months (range, 3-208 months), the overall survival (OS) and progression-free-survival (PFS) rates at 98 months were 82% (95%CI, 73-89) and 74% (95% CI, 64-82), respectively (Figure 1) . The cumulative incidence (CI) of grade II-IV and III-IV acute GVHD was 22% and 9%, respectively. The CI of chronic GVHD was 38%. Treatment-related mortality at 1 year was 9%. Patient demographic, disease characteristics, and transplant characteristics and their correlation with outcomes were evaluated. Disease status of > 1st relapse, >2 prior chemotherapies, duration of last remission prior to alloSCT < 1 year, ≥ 3 comorbidities, elevated LDH, acute II-IV GVHD, chronic extensive GVHD were associated with inferior OS. By multivariable analysis (MVA), duration of last remission prior to alloSCT (<1year) [HR 6.48 (1.28, 32.69); p=0.024]) and acute II-IV GVHD [HR 8.61 (2.99, 24.83); p<0.001] were associated with inferior OS. No significant prognostic factors on MVA for PFS, or risk for acute or chronic GVHD were noted for this cohort of patients. Conclusions: Nonmyeloablative allogeneic transplant can induce complete responses lasting over a decade in most patients with relapsed FL. Our initial findings published in 2008 were thus confirmed in a larger number of patients including those who received MUD transplants. BFR conditioning has been associated with significantly lesser myelosuppression and a faster neutrophil recovery than other regimens used, validating our initial observation in earlier reports.

Disclosures: Jabbour: Novartis: Research Funding; Pfizer: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Abbvie: Research Funding; Takeda: Consultancy, Research Funding. Bashir: Spectrum: Other: Advisory board; Amgen: Other: Advisory board; Celgene: Research Funding; Takeda: Other: Advisory board, Research Funding; KITE: Other: Advisory board. Oran: AROG pharmaceuticals: Research Funding; ASTEX: Research Funding; Celgene: Consultancy, Research Funding. Champlin: Otsuka: Research Funding; Sanofi: Research Funding.

*signifies non-member of ASH