Long-Term Survival for Myeloma after Autologous Stem Cell Transplantation.

Long-Term Survival for Myeloma after Autologous Stem Cell Transplantation.

S238 Abstracts / Biol Blood Marrow Transplant 26 (2020) S96 S255 Figure 2. (A) Week 4 post-treatment PET/CT showing flare vs persistent disease and (...

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Abstracts / Biol Blood Marrow Transplant 26 (2020) S96 S255

Figure 2. (A) Week 4 post-treatment PET/CT showing flare vs persistent disease and (B) 8 week post-treatment PET/CT showing significant interval resolution of disease with one new FDG avid lesion in left medial thigh in patient with AITL.

355 €m Autologous Stem Cell Transplant for Waldenstro Macroglobulinemia in the Era of Novel Therapies: Still an Underutilized Tool? Ricardo Daniel Parrondo MD1, Muhamad Alhaj Moustafa MD2, Prashant Kapoor MD3, Vivek Roy MD1, Craig Reeder MD4, Sikander Ailawadhi MD2. 1 Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL; 2 Division of HematologyOncology, Mayo Clinic Jacksonville, Jacksonville, FL; 3 Division of Hematology, Mayo Clinic, Rochester, MN; 4 Mayo Clinic, Scottsdale, AZ € m macroglobulinemia (WM) is a Background: Waldenstro rare and incurable lymphoproliferative disease. The advent of novel therapies such as proteasome inhibitors and monoclonal antibodies has expanded the therapeutic armamentarium for treatment of WM. Due to the rare nature of the disease, most reported studies on the use of autologous stem cell transplant (ASCT) in WM are small and retrospective in nature. Since the advent of novel agents, few studies have reported whether these agents influence the disease course in the ASCT setting. Herein we present outcomes of patients with WM who underwent ASCT at three Mayo Clinic sites. Methods: Records of all patients with WM who underwent ASCT between 8/2005 and 11/2017 were reviewed. Time-toevent analyses were performed from ASCT using the KaplanMeier method. Response criteria from the 6th International WM Workshop were used. Results: Patient characteristics are described in Table 1. Two patients had large cell transformation; one prior to ASCT and one post-ASCT. The overall response rate to transplant was 100% (3 complete responses [CR], 8 very good partial responses [VGPR] and 6 partial responses [PR]). After a median follow-up of 58 months, the median progression free survival (PFS) after ASCT was 66 months and the median overall survival (OS) was not reached (NR). The relapse rate was 65% (11 out of 17 patients relapsed). The treatment related mortality was 0% and relapse mortality was 12%. The 2 deaths in the cohort were the patients who had large cell transformation and they died at 18 and 25 m post-ASCT, respectively. The treatment immediately prior to transplant, irrespective of the use of rituximab (R), did

not impact the PFS (median PFS 47 m with prior R v 66 m without prior R, p=0.82, Fig. 1A). Similarly, prior exposure to a bortezomib (V)-based regimen did not impact the PFS (median NR v. 47 m, p=0.19 respectively, Fig. 1B). Achieving VGPR after ASCT did not result in superior PFS compared to patients who achieved a PR (47 m vs. NR, p=0.59, respectively, Fig. 1C). Patients who had ASCT after >2 lines of therapy had an inferior PFS compared to patients who had ASCT 2 lines of therapy (41 m vs. 112 m, p=0.03, respectively, Fig 1D). Patients with large cell transformation at any point, had inferior PFS after transplant compared to those who did not (10m vs. 66m, p<0.0001, respectively, Fig 1E). The median time to next treatment (mTTNT) after ASCT was 49 m. There were no differences in mTTNT whether patients achieved VGPR or PR after ASCT (49m vs. 39m, p=0.86, respectively, Fig 1F). Conclusions: ASCT for patients with WM is a safe and efficacious treatment modality with an ORR of 100% and affords eligible patients a median treatment-free interval of 4 years. The use of V or R prior to ASCT does not impact the depth of response or PFS after ASCT. To obtain the maximum PFS benefit, ASCT should be performed earlier in the disease course, prior to receiving more than 2 lines of therapy.

356 Long-Term Survival for Myeloma after Autologous Stem Cell Transplantation. Samer A. Srour MD, MS1, Denai R. Milton1, Qaiser Bashir MD1, Rohtesh S. Mehta MD, MPH, MS1, Neeraj Saini MD1, Stefan O. Ciurea MD1, Uday R. Popat MD1, Issa F. Khouri MD1, Partow Kebriaei1, Ruby Delgado1, Gabriela Rondon MD1, Elisabet Manasanch MD2, Krina Patel MD2, Hans C. Lee MD2, Elizabeth J. Shpall MD1, Robert Z. Orlowski MD2, Richard E. Champlin MD3, Muzaffar H. Qazilbash MD1. 1 Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX; 2 Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; 3 The University of Texas MD Anderson Cancer Center, Houston, TX Introduction: Multiple myeloma (MM) remains incurable with only a small proportion of patients (pts) surviving over 10 years (long-term survivors). It has been over 3 decades since the first autologous stem cell transplantation (ASCT) was done for MM at the University of Texas MD Anderson Cancer Center (MDACC). We sought from this study to describe patient and disease characteristics of long-term MM survivors after ASCT. Methods: We included consecutive pts who underwent their first ASCT at MDACC between January 1988 and December 2015. The primary objective was to assess and compare baseline characteristics and predictive factors for long-term vs short-term (died within10 years from diagnosis) MM survivors. We excluded MM survivors with <10 years of follow up from diagnosis. Associations between predictive factors and surviving > 10 years were assessed by logistic regression models. Results: Among 2176 pts who underwent their first ASCT during the study period, 1409 pts met the eligibility criteria of which 392 (28%) were long-term survivors and 1017 (72%) were short-term survivors. Only 24 and 43% of pts in the longterm and short-term survivor groups received proteasome inhibitor-based induction. Compared to short-term survivors, higher percentage of pts in the long-term survivor group were younger <65 (86%), had ISS Stage I (47%), standard-risk cytogenetics (96%), normal LDH (88%), and serum creatinine <2 mg/d (87%) at baseline. Majority of long-term survivors were relapse-free at 24 months from transplant (76%) compared to

Abstracts / Biol Blood Marrow Transplant 26 (2020) S96 S255

only 32% in the short-term survival group. On multivariable analysis, age, cytogenetic-risk status, race-ethnicity, and duration of remission after ASCT were significant predictors for surviving > 10 years (Table). ISS Stage III (OR 0.45, 95% CI 0.191.05; p=0.08) showed a trend towards shorter OS. Maintenance treatment was not significantly associated with surviving > 10 years. Median follow-up from diagnosis for the long-term survivor group was 13 years (10-30 years); among this group, the 15-year PFS rate was 19% (95% CI 14% - 23%) and the 15-year OS rate was 62% (95% CI 56% - 68%) (Figure 1). The cumulative incidence rates of relapse at 1, 3, and 5 years in the short-term survival group were 9%, 63%, and 82%, respectively, compared to 2%, 20%, and 40%, respectively, in the long-term survivor group (p<0.001) (Figure 2). Conclusions: ASCT is associated with durable responses and prolonged survival in a subgroup of MM pts irrespective of type of induction therapy and/or use of maintenance therapy. Duration of remission after transplant is the strongest predictor for long-term survival. Age <65 years, being African-American, and standard-risk cytogenetics were also associated with surviving more than 10 years.

(interquartile range, 0.6-3.5%); 15 of 77 (20%) had 3% proliferating pPC. Proliferating pPC poorly correlated with proliferating cPC percentage (R2 = .006). When separating patients with 3% and <3% proliferating pPC, characteristics, e.g. highrisk cytogenetics, were balanced (Table 1). Patients with 3% proliferating pPC had significantly worse Day 100 responses and a trend toward worse best-responses post-ASCT (Table 1). TNT was significantly shorter in patients with 3% proliferating pPC (16.8 vs. 23.9 months, p= .0287); OS was comparable (Figure 2). In a multivariate Cox proportional hazard model adjusting for proliferating cPC (2% vs. <2%), proliferating pPC 3% remained a significant predictor for TNT (hazard ratio 2.80, 95% confidence interval 1.25-6.27, p= .0126). Conclusion: Patients with multiple myeloma who failed to achieve CR by Day 100 post-ASCT with 3% proliferating pPC had significantly shorter TNT, independent of proliferating cPC. This is the first study to evaluate proliferating pPC as a prognostic marker, which could be a surrogate for a pro-proliferative BM microenvironment. References: 1. Sidiqi et al. BMT. 2019;54(3):442.

357 The Impact of Proliferating Polyclonal Plasma Cells on Outcome after Autologous Stem Cell Transplantation in Multiple Myeloma Kevin C. Miller1, Michael Timm2, Dragan Jevremovic MD, PhD2, Morie Gertz MD3, Francis Buadi MD3, Suzanne R. Hayman MD3, Martha Q. Lacy MD3, Angela Dispenzieri MD3, David Dingli MD3, Prashant Kapoor MD3, Wilson I. Gonsalves MD3, Taxiarchis Kourelis MD3, Eli Muchtar MD3, William J. Hogan MBBCh3, Shaji Kumar MD3. 1 Mayo Clinic School of Medicine, Rochester, MN; 2 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; 3 Division of Hematology, Mayo Clinic, Rochester, MN Introduction: Autologous stem cell transplantation (ASCT) is the standard-of-care for fit/younger patients with multiple myeloma. Outcomes are heterogeneous for those achieving less than a complete response (CR) after transplant; novel predictors of early relapse are needed to guide consolidation, maintenance and disease monitoring strategies. The postASCT proliferative index of clonal plasma cells (cPC) predicts for survival.1 In the present study, we evaluated nonmalignant proliferating polyclonal plasma cells (pPC) for an independent effect on outcome. Methods: From January 1 2013 to January 1 2014, 176 consecutive patients with multiple myeloma underwent their first ASCT at our institution and had a bone marrow (BM) specimen collected approximately 100 days post-ASCT. All BM was subject to multi-parametric flow cytometry using a BD FACS Canto IITM as previously described. Briefly, proliferating (S-phase) pPC were classified using DAPI staining and reported as a percentage of total pPC, which was calculated if there were at least 150 pPC/500000 events (Figure 1). Those with less than 150 pPC were deemed “non-evaluable.” Time to next therapy (TNT) was calculated from ASCT Day 0 to the initiation of a new therapy (not including maintenance or consolidation), with patients censored at time of last follow-up or death without further therapy. Overall survival (OS) was calculated from Day 0 to death, with living patients censored at time of last followup. Statistics were performed using R 3.5.2. Results: Responses at Day 100 were as follows: 71 (40%) CR, 48 (27%) very good partial response, 57 (33%) partial response or less. Among the 77 of 105 (73%) patients with
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Figure 1.

Figure 2A.