Patterns of Relapse Among Myeloma Patients Post-Autologous Stem Cell Transplant

Abstract Introduction: In younger patients that are transplant-eligible, autologous stem cell transplant (ASCT) prolongs overall survival based on several prospective randomized control trials. Nevertheless, ASCT is not a curative approach and majority of the patient's relapse, requiring further salvage therapeutic options. However, in the face of an ongoing paradigm shift in myeloma therapeutics, there is a significant knowledge gap regarding how patients relapse following ASCT. We analyzed the patterns of relapse among myeloma patients after ASCT. Methodology: We have evaluated a total of 975 patients that underwent ASCT during the period January 2008 through June 2014 from our myeloma database. 273 patients had documented evidence of first relapse post-ASCT on the laboratory parameters, radiologic or pathologic findings based on IMWG criteria for relapse. We categorized the relapses as biochemical vs symptomatic, and described their frequencies and characteristics. Median time of follow up from diagnosis is 68 months and from ASCT is 54 months. We used IBM SPSS version 23.0 to generate the survival statistics. Results: Median time from ASCT to relapse is 20 months. A total of 182 (66.7%) patients (105M, 77F) experienced biochemical relapse, while 91 (33.3%) patients (50M, 41F) had symptomatic relapse. More IgA patients (30.8% vs 23.1%, p=0.06) relapsed as symptomatic myeloma. While characterizing relapses, we did not find any differences in symptomatic relapses by the risk group [high risk (31.3%) vs standard risk (31.9%), p=0.193, ISS stage I (29.3%) vs II (32.9%) vs III (32.8%), p=0.807] or by maintenance [yes (30.7%) vs no (38.1%), p=0.211]. Among the patients that had a symptomatic relapse, presence of new bone lesions (52%) and anemia (42%) are the most common forms of relapse seen. Only 4% presented as hypercalcemia and 1% presented as renal failure illustrating the benefits of closer follow up. Overall survival is similar among patients that relapsed as biochemical or symptomatic relapse (log rank, p=0.105). More importantly, impressive median OS of 145 months from the ASCT among this entire cohort (at median follow up 54 months, figure 1). Conclusions: Two-thirds of the patients relapse as a biochemical relapse post-ASCT. The patterns of biochemical vs symptomatic relapses were similar among patients by maintenance, by risk status and also by the ISS stage. The significant improvement in OS among the entire cohort emphasizes the power of the new therapeutic salvage strategies aimed at gaining the survival advantage even among this selected group of patients undergoing early relapses. Disclosures Kaufman: Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Incyte: Consultancy; Pharmacyclics: Consultancy. Lonial:Novartis: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Onyx: Consultancy; Onyx: Consultancy; Merck: Consultancy; Janssen: Consultancy; BMS: Consultancy; BMS: Consultancy; Millenium: Consultancy; Celgene: Consultancy. Nooka:Spectrum, Novartis, Onyx pharmaceuticals: Consultancy.

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Improved Stem Cell Transplant Related Mortality for AL Amyloidosis At a Single Transplant Center

Blood ◽

10.1182/blood.v120.21.2016.2016 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2016-2016

Author(s):

Zandra K. Klippel ◽

Barry Storer ◽

William I. Bensinger ◽

Leona Holmberg ◽

Pamela S Becker ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Risk Stratification ◽

Research Funding ◽

Cardiac Involvement ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Al Amyloidosis ◽

Cell Transplant ◽

Entire Cohort

Abstract Abstract 2016 The role of AHSCT in AL amyloidosis is controversial. There is evidence that AHSCT offers long term disease control with high organ response rates, however, the only randomized phase III trial comparing transplant with conventional melphalan and dexamethasone therapy deemed transplant inferior. Better understanding of risk stratification for SCT candidacy has resulted in TRM rates are as low as 5.6% in some series. The goal of the current study was to evaluate the TRM rate for all consecutive patients who have undergone AHSCT for AL amyloidosis at institution. Special attention in evaluation of any detectable differences in TRM over the time period of this review was a major goal of this project. Retrospective review was performed of all patients with primary AL amyloidosis who have undergone AHSCT at our institution. The database captured patients from December 2001 and our study includes patients through February 2012. Patients who were diagnosed with secondary amyloidosis by the stem cell transplant service and/or referring oncologist were excluded. TRM was defined as death from any cause within 100 days post stem cell infusion. We then evaluated data from the entire cohort and divided it into two different time periods: 2001–2006 and 2007–2012. Thirty-nine patients had an initial AHSCT during the study period. Nine patients were enrolled in the SWOG 0115 trial which comprised tandem autoSCT using 100 mg/m2 of melphalan conditioning 3–6 months apart. Of those, 6/9 (66%) had both transplants. For purposes of this abstract we report on the data resulting from first transplantation only for patients in the SWOG 0115 trial. The median age at transplant for the entire cohort was 57.6 years old (39–74). Males represent 64% of the patients. Most of the patients had symptomatic involvement of one organ (48.7%) with 23% having more than 2 organs involved. There were 14 patients transplanted in the 2001–2006 period and 25 patients in the 2007–2012 period. Overall TRM for 2001–2012 was 5.1%. During the 2001–2006 period TRM was 14% (2/14 patients). No TRM occurred for patients transplanted from 2007–2012. Overall survival (OS) improved when separately comparing the two study periods. Overall survival was 64% at 3 years in the 2001–2006 cohort and 92% at 3 years in the 2007–2012 cohort. Patients in the 2007–2012 cohort include all patients enrolled to SWOG 0115. Sixty percent of patients reported for that period received <200mg/m2 melphalan for transplant conditioning. Eight of nine patients enrolled in SWOG 0115 received 100 mg/m2, one received 140mg/m2. Six patients treated on our institution's standard amylodosis SCT protocol received 140mg/m2 conditioning. The remaining ten patients received 200mg/m2 melphalan. Patients in the 2007–2012 period were more likely to receive induction treatment prior to transplant with novel regimens (72% vs 21% p=0.003). In addition, these patients were more frequently diagnosed with amyloid cardiac involvement. For purposes of this abstract amyloid cardiac involvement is defined according to whether or not the SCT team concluded on the basis of history, physical examination and available ancillary data (including echocardiography) that the patient had amyloidotic cardiac disease (40% vs 14% p=0.15). All patients had echocardiography pre-AHSCT. The mean Inter Ventricular Septum (mIVS) thickness was 14.5 mm in the 2007–2012 period vs. 11.7 mm in the 2001–2006 one p=0.004. Univariate analysis of risk factors affecting improved OS identified year of transplant (>2006; p=0.03), number of treatments pre-transplant (>1; p=0.04), and time from diagnosis to transplant (>4mo; p=0.05) as factors associated with improved survival. Number of organs involved (>1; p=0.06) showed a trend towards worse survival. In conclusion, our single institution data demonstrates a reduction in TRM over the past 5 years. Reasons for improvement in TRM are under investigation and may include better risk stratification, better supportive care (including frequent hospitalization for cardiac monitoring in high-risk patients) and improvement in pre-AHSCT performance status for those patients receiving induction therapy with novel agents. Figure: Comparison of overall survival of patients with AL amyloidosis after autologous stem cell transplant based on year of transplant. Figure:. Comparison of overall survival of patients with AL amyloidosis after autologous stem cell transplant based on year of transplant. Disclosures: Holmberg: Millenium: Research Funding; Otsuka: Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Sanofi: Research Funding.

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Improved Survival for Patients Undergoing Autologous Stem Cell Transplant for Primary CNS Lymphoma in First or Later Remission.

Blood ◽

10.1182/blood.v114.22.1222.1222 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1222-1222 ◽

Cited By ~ 1

Author(s):

Patrick B Johnston ◽

Ivana N Micallef ◽

Stephen M Ansell ◽

David J Inwards ◽

Luis F. Porrata ◽

...

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

Stem Cell ◽

Stem Cell Transplant ◽

Primary Cns Lymphoma ◽

Autologous Stem Cell Transplant ◽

Cns Lymphoma ◽

Cell Transplant ◽

Additional Therapy

Abstract Abstract 1222 Poster Board I-244 Background Survival for patients with primary CNS lymphoma (PCNSL), in general, is poor with patients requiring frequent chemotherapy treatments or receiving whole-brain radiation therapy, which can potentially result in significant neurologic decline and dementia. Because of the improved survival of high risk patients with aggressive lymphoma undergoing autologous stem cell transplant (ASCT), we began ASCT for patients with PCNSL in first or later remission with chemotherapy sensitive disease. We now update on outcomes of patients who have had at least 100 day follow up post ASCT. Baseline characteristics Between June, 2000 and January, 2009, 22 patients underwent ASCT for PCNSL. Median age at transplant was 50 years old (range 26-67). Median number of prior treatments 1 (range 1-3). Median time from diagnosis to transplant was 7.2 months (range 2.9 to 75.8). Median International Extranodal Working Study Group Prognostic Score: 2 (range 0-3). Disease status at transplant: First CR 10 patients, later CR or PR 12 patients. Results Twenty-two patients underwent ASCT for PCNSL and have a minimum of 100 days follow-up. All patients received BEAM conditioning. Median follow up post-transplant was 30 months (range 3-107 months). Eight patients have relapsed at a median of 217 days (range 40-1349). Of the patients who relapsed, four have died of disease progression and the remaining four are alive after additional therapy. Median overall survival from diagnosis or transplant has not been reached. Median progression free survival from transplant was 70 months. Conclusions Although limited by patient selection and retrospective biases, this review suggests that ASCT for PCNSL demonstrates improved overall survival when compared to historical controls with similar PCNSL Prognostic Scores (2 year survival for patients from diagnosis with PS 2-3 was 48% in a prior published study). ASCT in first remission in patients with PCNSL appears promising and may limit the need for additional therapy which can be myelosuppressive or result in neurologic decline secondary to radiation therapy in patients who are appropriate candidates. Disclosures No relevant conflicts of interest to declare.

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Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽

10.1182/blood.v120.21.4554.4554 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4554-4554

Author(s):

Catherine Garnett ◽

Chrissy Giles ◽

Osman Ahmed ◽

Maialen Lasa ◽

Holger W. Auner ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Stem Cell Transplant ◽

Progression Free Survival ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Free Survival

Abstract Abstract 4554 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma, resulting in improved survival and response rate compared to conventional chemotherapy. Disease relapse, however, remains almost inevitable and thus the role of two successive (tandem) autologous stem cell transplants has been evaluated in chemorefractory patients as a means of prolonging duration of disease response. We retrospectively analysed the results of nine patients with chemorefractory disease treated at a single UK institution who received tandem ASCT between January 1998 and February 2009. There were six men and three women. Median age at diagnosis was 56 years (range, 42–65 years). Paraprotein isotype was IgG in eight patients and IgA in one patient. Median serum paraprotein level was 41g/L (range 12–73g/L) at presentation. At time of 1st transplant six patients were in stable disease (SD) and three had evidence of progressive disease. Conditioning melphalan dose was 140mg/m2 in all but two patients who received 110mg/m2 and 200mg/m2. Median time between transplants was 3.7 months (range 2.3–6.4 months) with PR and SD being observed in 2/9 and 7/9 patients at time of 2nd transplant. None of the patients reached complete response (CR). One patient received melphalan 140mg/m2 prior to 2nd transplant. The remaining patients received melphalan 200mg/m2. Median follow up after tandem transplant was 54.3 months (range 15.6 –143.6 months). No treatment related mortality was reported. At the time of analysis, six patients were still alive and under follow up with an overall survival (OS) figure for the group of 52% at 10 years from diagnosis (Figure 1). Median progression free survival (PFS) was 20 months from 2nd transplant (range 6.7–62.6 months) (Figure 2). Tandem autologous stem cell transplant in chemorefractory patients has resulted in overall survival similar to autologous stem cell transplant in chemosensitive patients and should be considered in patients with chemorefractory disease. Figure 1: Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 1:. Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 2: Progression free survival following tandem transplant Figure 2:. Progression free survival following tandem transplant Disclosures: No relevant conflicts of interest to declare.

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Autologous stem cell transplant for primary CNS lymphoma results in prolonged progression free and overall survival

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7623 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7623-7623

Author(s):

P. B. Johnston ◽

B. P. O’Neill ◽

S. M. Ansell ◽

D. J. Inwards ◽

L. F. Porrata ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplant ◽

Primary Cns Lymphoma ◽

Autologous Stem Cell Transplant ◽

Cns Lymphoma ◽

Cell Transplant ◽

Free Survival ◽

Additional Therapy

7623 Background: Survival for patient with primary CNS lymphoma (PCNSL), in general, is poor with patients requiring frequent chemotherapy treatments or receiving whole-brain radiation therapy, which can potentially result in significant neurologic decline and dementia. Because of the improved survival of high risk patients with aggressive lymphoma undergoing autologous stem cell transplant (ASCT), we began ASCT for patients with PCNSL in first or later remission with chemotherapy sensitive disease. We now report on outcomes of patients who have had at least 1 year follow up post ASCT. Methods: Between June, 2000 and September, 2004, 11 patients underwent ASCT for PCNSL. The medical records of consenting patients were abstracted for the following information. Median age at transplant was 47 years old (range 30–67). Median number of prior treatments 1 (range 1–3). Median time from diagnosis to transplant was 7.5 months (range 2.9 to 75.8). Median International Extranodal Working Study Group Prognostic Score: 2 (range 0–3). Disease status at transplant: First CR 5 patients, later CR or PR 6 patients. Results: Eleven patients underwent ASCT for PCNSL and have a minimum of 1 year follow-up. All patients received BEAM conditioning. Median follow up was 28.3 months. Four patients have relapsed at a median of 200 days (range 40–523). Of the patients who relapsed, one has died of disease progression and the remaining three are alive after additional therapy. Median overall survival and progression free survival from transplant have not been reached. Two year overall and event free survival are 89% and 61%, respectively. Conclusions: Although limited by patient selection and retrospective biases, this review suggests that ASCT for PCNSL demonstrates improved overall survival when compared to historical controls with similar PCNSL Prognostic Scores (2 year survival for patients from diagnosis with PS 2–3 was 48% in a prior published study). ASCT in first remission in patients with PCNSL appears promising and may limit the need for additional therapy which can be myelosuppressive or result in neurologic decline. No significant financial relationships to disclose.

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Efficacy of Daratumumab Containing Regimens Post Lenalidomide Maintenance in Transplant Eligible Patients: Real-World Experience from the Canadian Myeloma Research Group Database

Blood ◽

10.1182/blood-2020-133372 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 26-27

Author(s):

Hira S Mian ◽

Christine Eisfeld ◽

Christopher P. Venner ◽

Victor Jimenez-Zepeda ◽

Cyrus Khandanpour ◽

...

Keyword(s):

Stem Cell ◽

Real World ◽

Research Group ◽

Research Funding ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

P Value ◽

Cell Transplant ◽

Second Line

Introduction Lenalidomide maintenance following autologous stem cell transplant (ASCT) remains a standard of care among transplant eligible patients with newly diagnosed multiple myeloma (NDMM). Many previous clinical trials done in patients following one prior line of therapy either excluded patients progressing on lenalidomide or included a very small proportion of these patients. Given the paucity of data in this setting, the optimal management of patients progressing on lenalidomide maintenance remains unknown. Daratumumab-containing triplet regimens have recently been introduced for these patients, typically in combination with pomalidomide (DPd), lenalidomide (DRd), or bortezomib (DVd). To our knowledge, there is no prospective data to allow comparison of the efficacy of these three regimens in patients progressing on lenalidomide maintenance, which is an increasingly common clinical scenario. Understanding the comparative efficacy, tolerability and toxicity of these regimens in patients progressing on lenalidomide maintenance in the 'real-world' is needed in order to help clinicians make appropriate decisions and guide future studies. Methods The Canadian Myeloma Research Group Database (formerly known as the Myeloma Canada Research Network Database, MCRN-DB) is a prospectively maintained disease specific database with over 7000 patients enrolled from 14 academic sites across Canada with legacy data collected from 2007. The Munster Myeloma database collects myeloma specific information in a German academic center and currently contains data from 800 patients collected from 2005. All consecutive patients treated with daratumumab based regimens in second line following relapse on lenalidomide maintenance were included in the analysis from the two databases analyzed up to 30/06/2020. Results A total of 1380 NDMM patients on lenalidomide maintenance post autologous stem cell transplant were identified in the two databases. From them, 73 patients were included in this analysis as they were treated with daratumumab containing regimen in second line. Specifically, 18 (24.7%) of these patients were treated with DPd, 32 (43.8%) patients with DRd, and 23 (31.5%) patients with DVd. The baseline characteristics, maintenance details, post-maintenance response rates and toxicity for each regimen are shown in Table 1. The median follow-up for the cohort from the time of daratumumab initiation was 8.3 months (range 0.4 - 40.0). Although, a higher proportion of patients in the DPd arm obtained a CR/VGPR compared to DRd or DVd, it did not reach statistical significance (p-value 0.06). The median PFS of the entire cohort was 16.96 months (95% CI 11.47-23.44). The median PFS of the individual regimens was as follows: DPd 17.65 months, DRd not reached and DVd 11.47 months as demonstrated in Figure 1 (p-value =0.46). Conclusion In summary, our results show that daratumumab-based regimens are effective among patients progressing on lenalidomide maintenance in the real world. Despite the small sample size, the results presented here are in line with recent sub-analyses of phase III studies examining the common daratumumab-based regimens used in this setting (CASTOR with median PFS of DVd between 7.8 months in all lenalidomide refractory patients and 27 months in all patients in first relapse; MM014 with median PFS of DPd after lenalidomide refractoriness of 21.8 months). The efficacy of DRd, in which daratumumab is added to an increased dose of lenalidomide, is notable and warrants further evaluation to identify which patients are most likely to benefit. Additional studies with longer follow-up are required to assess the optimal daratumumab-based regimen to be used in this growing population of patients relapsing after lenalidomide maintenance. Disclosures Mian: Janssen: Consultancy, Honoraria; Celgene: Consultancy; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy. Venner:Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. Jimenez-Zepeda:Janssen, Celgene, Amgen, Takeda: Honoraria. McCurdy:Sanofi: Honoraria; GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Sebag:Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding. Song:Celgene: Research Funding; Celgene, Janssen, Amgen, Takeda: Honoraria. Leblanc:Celgene: Research Funding; Celgene Canada; Janssen Inc.; Amgen Canada; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. White:Karyopharm: Honoraria; Antengene: Honoraria; GSK: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Stakiw:Roche: Research Funding; Celgene: Honoraria; Lundbeck: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; BMS: Honoraria. Louzada:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Kotb:Karyopharm: Current equity holder in publicly-traded company; Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Merck: Honoraria, Research Funding; Sanofi: Research Funding. Reece:Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy; Amgen: Consultancy, Honoraria; Millenium: Research Funding; BMS: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Otsuka: Research Funding.

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Treatment and Management of Chronic Myelogenous Leukemia in Patients Cared for in a Large HMO

Blood ◽

10.1182/blood.v124.21.1310.1310 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1310-1310

Author(s):

Reina Haque ◽

Jiaxiao Shi ◽

Joanie Chung ◽

Chantal C Avila ◽

Lei Chen ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Health Plan ◽

Research Funding ◽

Stem Cell Transplant ◽

Chronic Phase ◽

Cell Transplant ◽

First Line ◽

Median Length

Abstract Introduction CML management has rapidly changed in the last decade. Data are critically needed to characterize disease treatment, management, and drug use (particularly TKIs, tyrosine kinase inhibitors) to ultimately inform how to improve outcomes in patients with CML. Our objective was to describe practice trends in a large community based health plan serving over 3.2 million members in southern California, Kaiser Permanente (KPSC). Methods Patients were identified from the health plan’s NCI-SEER affiliated cancer registry. The cohort consisted of 257 CML adult patients (18+ years, chronic phase, no prior cancer history) all diagnosed between January 2001 and December 2012 and followed through December 31, 2013. We collected data from electronic health records and chart reviews including demographics, TKI use and adherence, healthcare utilization and clinical outcomes. Medication possession ratio (MPR) was used to measure adherence, calculated as the number of days supplied divided by the number of days between first and last dispense date of any TKI. We classified patients into MPR>90% (indicates good adherence) and MPR<90%. Discontinuation was ascertained from providers’ notes in the medical charts. Results Of the 257 patients with newly diagnosed chronic phase CML, 111 were female (43%). About 58% (n=148) were non-Hispanic Whites, and 23% (n=59) were Hispanic. About half (48%, n=124) had one or more existing comorbidities. Over 90% of the cohort initiated TKI therapy within 3 months of diagnosis, and mean MPR was 88% (s.d. 18%). About two-thirds of the patients (63%, N=157) had an MPR>90% for TKI use. Virtually all patients (96%) started on imatinib. Of the 59 cases diagnosed 2010-2012, only 14 used dasatinib or nilotinib as first line therapy. Half of the cohort (n=107) discontinued first line treatment (mainly imatinib). Reasons for discontinuation included general adverse effects (e.g., skin rash, muscle cramps), cardiovascular, lung or abdominal effects (n=41); incomplete cytogenetic or molecular response (n=38); drug non-response, provider recommended, not compliant (n=21); or BMT/stem cell transplant (n=7). The cohort was followed a maximum of 13 years (mean 5.1 years, s.d. 3.1 years). The total number of hospitalizations was 351 among patients diagnosed 2001-2006; 113 diagnosed 2007-2009; and 71 diagnosed 2010-2012. The median length of each hospitalization was 10 days (s.d. 30.6) during the follow-up years. Among imatinib users, the median number of overall outpatient visits per year varied from 20 visits/year for patients diagnosed 2001-2006 to 11 visits/year for patients diagnosed 2010-2012. Overall, 18 patients underwent bone marrow and/or stem cell transplant (all diagnosed 2001-2006). We examined progression and overall survival in patients diagnosed in 2001-2006 and exposed to imatinib. The rate of progression to accelerated phase or blast crisis was lower in patients with MPR>90% (10.0/1,000 person-years) than with MPR<90% (14.2/1,000 person-years). Similarly, patients with MPR>90% had a lower mortality rate (25.9/1,000 person-years) than patients with MPR<90% (39.2/1,000 person-years). Kaplan Meier curves for overall survival also demonstrate better survival, but not significantly (log rank P=0.35), among those with MPR>90%. Figure 1 Figure 1. Discussion Most patients initiated TKI therapy within 90 days of diagnosis in this health plan. Our results show median length of each hospitalization was 10 days across all follow-up time. Despite having full pharmacy coverage, the percent of subjects with MPR>90% was moderate (64%). Our results also suggest that subjects with MPR>90% for TKIs had lower progression rates and greater overall survival, but the results were not significant, and need to be confirmed in a larger study. Next steps include examining the frequency of cytogenetic and molecular testing and how this might impact outcomes, and factors associated with lower TKI medication possession ratios. Disclosures Haque: Novartis: Research Funding. Shi:Novartis: Research Funding. Chung:Novartis: Research Funding. Avila:Novartis: Research Funding. Chen:Novartis: stock options Other. Schottinger:Novartis: Research Funding.

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Outcome of Patients with Hodgkin Lymphoma Treated with Brentuximab Vedotin for Relapse after Autologous Stem Cell Transplant: A Retrospective Analysis of the LWP-EBMT

Blood ◽

10.1182/blood-2019-131410 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4018-4018

Author(s):

Nikesh Dhiraj Chavda ◽

Stephen Robinson ◽

Ariane Boumendil ◽

Irma Khvedelidze ◽

Hervé Finel ◽

...

Keyword(s):

Stem Cell ◽

Hodgkin Lymphoma ◽

Median Time ◽

Research Funding ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Brentuximab Vedotin ◽

Cell Transplant ◽

Travel Grant

Around half of patients with Hodgkin Lymphoma (HL) who progress or relapse through first line therapy can be cured with salvage chemotherapy followed by autologous stem cell transplant (ASCT). However, this leaves approximately 50% of patients that will relapse after ASCT. The pivotal phase II SG035-00303 trial demonstrated that these patients can be successfully treated with Brentuximab Vedotin (BV), and a proportion of them can be long term free of disease without any further intervention. The objective of the current study was to investigate whether these findings were borne out in the real world via interrogation of the EBMT registry. We retrospectively analysed data for 101 patients with HL who had BV as their first treatment for relapse after ASCT from 2012 to 2019. The median age at ASCT was 34 years (range: 19-65), 60% being male and with 62% being in complete response (CR) at the time of ASCT. Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) was the most common conditioning regimen, having been employed in 72% of the cases. The median time from ASCT to relapse was 10.1 months (interquartile range (IQR): 6.1-25.1). The median time on BV was 3.4 months (IQR: 2.1-5.24). BV treatment resulted in a best overall response rate (ORR) of 59% with a CR rate of 37%. At last follow-up only 2 patients remain on treatment with BV. The main reason for discontinuation of BV was progression which occurred in 37% of the patients. In 32 cases (33%) the treatment was stopped electively to proceed to a second transplant, and overall nearly a quarter (22%) completed the full treatment course. Only 5% of patients stopped due to toxicity (peripheral neuropathy 2 and neutropenia, infusion reaction and other, 1 each). Further therapy was given after BV in over half of evaluable patients (58%), with check point inhibitors (CPIs) being the most common agents used (24% of these). Nearly two thirds (64/101) of the patients received a second transplant, which were nearly all allogeneic stem cell transplant (alloSCT, 59/64), and most of these (49/59) with reduced intensity conditioning (RIC). 26% of the alloSCT recipients experienced grade II-IV acute graft versus host disease (GvHD) and 25% developed chronic GvHD. At last follow up, 62% of all patients were alive with a median follow-up of 25 months after starting BV. Of these, 27 had received a second transplant, who were mostly in CR at last follow up (26/27) and a further 22 had relapsed. There were 11 patients of the 63 still alive who continued to be responding to BV without further therapy with a median duration of response of 30 months. In conclusion BV use for relapse after ASCT was well tolerated generally, with only a minority of patients stopping treatment due to toxicity. However, although almost two thirds of the patients achieved a response, further treatment was often needed after BV, notably with CPIs and most patients were consolidated with a RIC alloSCT. These results confirm that only a minority of patients can achieve a durable remission with BV alone. Disclosures Brice: Takeda France: Consultancy, Honoraria; Millennium Takeda: Research Funding; BMS: Honoraria. Blaise:Molmed: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria. Stamatoullas:Celgene: Honoraria; Takeda: Consultancy. Robak:Takeda: Consultancy, Research Funding; UCB: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grant, Research Funding; Amgen: Consultancy, Other: Travel grant; Roche: Consultancy, Other: Travel grant, Research Funding; Abbvie: Consultancy, Honoraria, Other: Travel grant, Research Funding; Gilead: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Acerta: Research Funding; Morphosys AG: Research Funding. Wahlin:Roche and Gilead: Consultancy.

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Phase 2 Trial of LDE225 and Lenalidomide Maintenance Post Autologous Stem Cell Transplant for Multiple Myeloma

Blood ◽

10.1182/blood-2019-132035 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1905-1905

Author(s):

Francis K. Buadi ◽

Martha Q. Lacy ◽

Angela Dispenzieri ◽

Gabriela Perez ◽

Morie A. Gertz ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Maintenance Therapy ◽

Research Funding ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

High Dose ◽

Cell Transplant ◽

Grade 3

Background: Lenalidomide maintenance therapy post-autologous stem cell transplantation (ASCT) is associated with improved progression-free survival (PFS) and possibly overall survival in multiple myeloma (MM). However, almost all patients do relapse as a result of residual multiple myeloma cells that remain after the high-dose chemotherapy. In the myeloma setting it has been found that the hedgehog (Hh) pathway is essential for maintaining a subset of tumor causing stem cells. LDE 225 (Sonidegib) is a potent selective oral bioavailable antagonist of Smoothened (SMO), a component of the Hh signaling pathway. In in vitro experiments, LDE225 treatment of myeloma cell lines resulted in a modest inhibition of cell proliferation at increasing doses. When LDE225 was combined with lenalidomide, a more than additive effect was observed in terms of cell proliferation, an effect that was more pronounced in the context of myeloma cell lines growing in co-culture with marrow derived stromal cells. These findings form the basis of evaluation of LDE 225 as a strategy to enhance the activity of lenalidomide in the post-transplant maintenance setting. The minimal residual state post SCT provides the most optimal situation for evaluation of a drug that is likely to work by inhibiting the tumor cells that escaped high dose therapy. Methods: Multiple myeloma patients without evidence of progression, who were 60 - 120 days after a single autologous stem cell transplant (SCT), performed within 1 year of diagnosis were eligible for the study. Maintenance therapy was started approximately 3 months after SCT. Treatment consisted of lenalidomide 10 mg days 1-21 and LDE225 400 mg days 1-28 in 28-day cycles for a total of 18 cycles. The goal of the study was to assess toxicity of this combination, complete response rate (CR) progression free survival (PFS) at 1 and 2 year and overall survival (OS). CR and PFS were estimated using an exact binomial distribution and Kaplan Meier curves respectively. Results: A total of 28 patients were accrued from Jan 2014 to Aug 2016, 1 patient canceled prior to treatment and 1 patient was deemed ineligible resulting in 26 evaluable pts for CR and PFS. The median age of all pts (n=26) was 60 years (range 43-69) and 50% were males. Seventy-three percent of patients reported one treatment regimen prior to SCT, while 27% reported 2 or more prior regimens. The other characteristics of the patient are summarized in Table 1. Twenty seven pts received at least one cycle of treatment and are evaluable for toxicities (AE). Patients were treated for a median of 12.5 (range 1-18) cycles. While 10 pts (38.5%) completed protocol treatment (18 cycles), the remaining 16 pts went off treatment due to AEs (6, 23%), disease progression (3, 11.5%), refusal of further treatment (3, 11.5%) and other reasons (4, 15.4%). A grade 3 or higher AE at least possibly attributed to either drug was seen in 63%. Grade 3+ hematologic toxicities were noted in 30%, with 7% neutropenia and 4% thrombocytopenia. Notable grade 2+ non-hematologic toxicities with more than 5% incidence were dysgeusia 22%, alopecia 11%, and anorexia 7%. Grade 3+ non-hematologic toxicities were fatigue, myalgia and arthralgia each at 7%. The CR rate in evaluable patients was 46% (5 CRs and 7 sCRs) with a 95% CI of 27% - 66%. CR rate improved from 31% to 46%. VGPR or better improved from 42% to 85%. The 24-month PFS (time from SCT to progression or death due to any cause) was 73% (95% CI: 57.9 - 92.3%) with a median time to censoring of 38 months. Conclusion: Lenalidomide in combination with LDE225 as posttransplant maintenance therapy was associated with some toxicity but manageable. The combination improved the depth of response after autologous stem cell transplant. Long-term follow-up is needed to determine overall survival. Disclosures Lacy: Celgene: Research Funding. Dispenzieri:Celgene: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Akcea: Consultancy; Alnylam: Research Funding. Gertz:Ionis: Honoraria; Alnylam: Honoraria; Prothena: Honoraria; Celgene: Honoraria; Spectrum: Honoraria, Research Funding; Janssen: Honoraria. Kapoor:Glaxo Smith Kline: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Celgene: Honoraria; Sanofi: Consultancy, Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Russell:Imanis: Equity Ownership. Kumar:Janssen: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy, Research Funding. OffLabel Disclosure: Sonidegib (LDE 225) is a selective oral bioavailable antagonist of Smoothened (SMO), a component of the hedgehog signaling pathway.

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Results of the 6-Year Follow-up of the Gimema AML1310 Trial: A Risk-Adapted, MRD-Directed Therapy for Young Adults with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽

10.1182/blood-2021-147200 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2359-2359

Author(s):

Adriano Venditti ◽

Alfonso Piciocchi ◽

Raffaele Palmieri ◽

Valentina Arena ◽

Anna Candoni ◽

...

Keyword(s):

Stem Cell ◽

Research Funding ◽

Stem Cell Transplant ◽

Residual Disease ◽

Disease Free Survival ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

To Receive

Abstract Background: In the AML1310 trial, we applied a comprehensive AML risk assessment, based on the integration of cytogenetic/genetic data and measurable residual disease (MRD) status, to optimize patients' (pts) therapeutic post-remission allocation. By doing so and using the NCCN2009 risk-stratification, favorable-risk (FR) pts (NPM1 mut/FLT3-ITD wt or CBF positive without c-Kit mutations) were to receive an autologous stem cell transplant (AuSCT); poor-risk (PR) pts (adverse karyotype or FLT3-ITD mut) were to receive an allogeneic stem cell transplant (ASCT); intermediate-risk (IR) pts (intermediate karyotype or FLT3-TKD mut or CBF positive with c-Kit mut) were to receive AuSCT or ASCT depending on the levels of MRD, measured by flow cytometry after consolidation therapy. Allocation to ASCT required the procedure to be performed whatever the source of stem cells (identical sibling, unrelated, cord blood, haploidentical). At that stage of analysis, 2-year overall (OS) and disease-free survival (DFS) of the whole series was 56% and 54%, respectively. Two-year OS and DFS were 74% and 61% in the FR category, 42% and 45% in the PR category, 79% and 61% in the IR MRD-negative category, 70% and 67% in the IR MRD-positive category (Venditti, Blood 2019:134(12);935-945) . Aims: With an extended median follow-up of 6 years, we wanted to evaluate the long-term impact on outcome of the strategy explored in the AML1310 trial. Specifically, we meant to analyze long-term duration of OS and DFS according to the category of risk, and the corresponding post-remission therapy delivered. Results: Three hundred-61/500 patients (72%) achieved a CR, 342/361 completed the consolidation phase and were treatment allocated: 165 (48%) to ASCT (122 PR, 43 IR MRD-positive) plus 23 rescued after salvage therapy, for a total of 188 candidates; 150 (44%) to AuSCT (115 FR, 35 IR MRD-negative) plus 27 IR patients (8%) with no leukemia-associated phenotype, for a total of 177 candidates. Overall, 110/177 (62%) and 130/188 (71%) AuSCT or ASCT candidates received it, respectively. Median OS and DFS was 3.1 and 2.9 years, respectively. Probability of 6-years OS and DFS of the whole series was 43.6% and 43.1%, respectively; cumulative incidence of relapse (CIR) was 39.7%. Probability of 6-years OS and DFS were 58.5% and 50.1% in the FR category; 35.4% and 38.0% in the PR category; 43.1% and 45.7% in the IR category. Probability of 6-year OS and DFS of patients with no LAIP detected was 32.5% and 29.1% (Fig.1 A-B). We did not observe difference in OS and DFS between the IR-MRD negative and IR-MRD positive category: 56.6% vs 62.3% and 51.6% vs 48.6%, respectively. Six-year CIR was 42.2%, 37.6% and 35.8% in the FR, PR and IR category, respectively (Fig. 1 C). Six-year CIR of patients with no LAIP detected was 50% (Fig.1 C). Six-year CIR and non relapse mortality (NRM) of transplanted patients was 35% and 15.8%, respectively (Fig.1 D). Conclusions: With an extended follow-up of 6 years, the present analysis confirms the long-term advantage of adopting a risk-adapted, MRD-directed strategy to implement the post-remission therapeutic decision. For patients belonging to the FR or IR-MRD negative category, an excess of toxicity was prevented by delivering an AuSCT. This is also in keeping with the ELN2017 recommendations, suggesting that AuSCT still has a role in selected situations. On the other hand, the vast majority of PR and IR-MRD positive patients received an ASCT, with a remarkable 6-year OS and DFS benefit. The effectiveness of such an approach translated in a low NRM in transplanted patients. Six-year OS, DFS and CIR of no LAIP patients also confirm that the choice of AuSCT was suboptimal and that in this situation ASCT should have been preferred. Based on the present knowledge, an MRD-directed approach is being explored also in FR patients, in the GIMEMA AML1819 trial. Figure 1 Figure 1. Disclosures Venditti: Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding. Luppi: Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Gilead Science: Honoraria, Other: Travel grant; Daiichi-Sankyo: Honoraria; Jazz Pharma: Honoraria. Voso: Celgene/BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz: Consultancy, Honoraria, Speakers Bureau; Abbvie: Speakers Bureau; Novartis: Speakers Bureau. Vignetti: Novartis: Honoraria; Incyte: Honoraria; Amgen: Consultancy, Honoraria. Buccisano: Novartis: Honoraria, Speakers Bureau.

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