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

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

Blood ◽

10.1182/blood.v128.22.4524.4524 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4524-4524

Author(s):

Prashanth Kumar ◽

Nisha Joseph ◽

Dhwani Almaula ◽

Lawrence H Boise ◽

Jonathan L. Kaufman ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Research Funding ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Biochemical Relapse ◽

Entire Cohort ◽

Symptomatic Relapse

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 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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Outcome After Failure to Second Generation Thyrosine Kinase Inhibitors(TKI) Treatment as Frontline Therapy for Patients with Chronic Myeloid Leukemia (CML) In Chronic Phase(CP).

Blood ◽

10.1182/blood.v116.21.3442.3442 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3442-3442

Author(s):

Alireza Eghtedar ◽

Hagop Kantarjian ◽

Elias Jabbour ◽

Susan O'Brien ◽

Alfonso Quintas-Cardama ◽

...

Keyword(s):

Stem Cell ◽

Research Funding ◽

Stem Cell Transplant ◽

Cytogenetic Response ◽

Initial Therapy ◽

Subsequent Treatment ◽

Cell Transplant ◽

2Nd Generation ◽

Frontline Therapy

Abstract Abstract 3442 Background: Imatinib has been the standard frontline therapy for patients with CML in early CP. 2nd generation TKIs (nilotinib, dasatinib) have been reported to be more effective than imatinib as frontline therapy in rates of response and transformation. Nilotinib has received regulatory approval for this indication and others (dasatinib, bosutinib) may come soon. Although fewer patients are expected to experience failure to therapy with the use of these agents, these patients will represent a management challenge. The characteristics, management and outcome of patients who fail therapy with 2nd generation TKI used as initial therapy has not been reported. Aim: To analyze the characteristics of patients who fail therapy with 2nd generation TKI used as initial therapy, their management, and outcome after failure to initial therapy. Methods: Two parallel studies of 2nd generation TKI as initial therapy for CML early CP are being conducted at MDACC, one with nilotinib and one with dasatinib. The study with nilotinib includes also patients in accelerated phase (AP) that have received no other prior therapy. The records of all patients who were taken off therapy from these trials were reviewed to investigate the reasons for failure, subsequent management and outcome. Results: A total of 172 pts have been treated with dasatinib (n=82) or nilotinib (n=90; 9 in AP) since 2005. After a median follow-up of 18.9 months, 23 pts (14%) have discontinued therapy: 13 (16%) pts in the nilotinib study (2 of them treated in AP), and 10 (12%) in the dasatinib study. Their median age 48 years (range:19–73) and they had received therapy with nilotinib or dasatinib for a median of 5.2 (0.03-48) months. Reasons for nilotinib treatment discontinuation include: toxicity 4 pts (elevated lipase, acute pancreatitis + atrial fibrillation, pericardial effusion and acute renal failure, one each), transformation to blast phase (BP) 3 pts (2 of them treated in AP), and other reasons 6 pts (2 each for insurance issues, patient request and non-compliance). Reasons for discontinuation of dasatinib include: toxicity 5 pts (2 pleural effusion, 1 prolonged thrombocytopenia, 1 bone pain, 1 congestive heart failure), 2 pts for loss of response, and 3 pts for pts' choice. Best response to frontline treatment with nilotinib or dasatinib was 6 (26%) pts major molecular response, 6 (26%) pts complete cytogenetic response, 1 (4%) pt partial cytogenetic response, 3 (13%) pts minor cytogenetic response, 1 (4%) pt with no response and 6 (26%) pts nonevaluable. At the time of failure 18 pts were in CP, 4 pts in BP (one pt transformed shortly after discontinuation) and 1 AP. At the time of treatment interruption, 14 pts had BCR-ABL sequencing and 2 were found to have mutations (F359C, Y253H); 3 pts had new additional chromosomal abnormalities (ie, clonal evolution). Subsequent treatment after failure to initial therapy include: imatinib in 8 pts, nilotinib in 2 pts, dasatinib 1 pt, Hyper CVAD with dasatinib 1 pt, Hyper CVAD with imatinib 1 pt, stem cell transplant 2 pts, bafetinib 1 pt, and unknown 4 pts (lost to follow-up). One pt died shortly after failure without further therapy. Best response to subsequent therapies were 1 pt with CMR (after stem cell transplant), 7 pts with MMR (3 pts after imatinib, 1 pt after dasatinib, 1 pt after nilotinib, 1 pt after Hyper CVAD with imatinib and 1 pt after stem cell transplant), 1 pt CHR, 1 pt minor CyR, 3 pts without response, and 8 pts were not evaluable. Of the 5 pts that achieved MMR with subsequent TKI, all were in CP and had discontinued initial therapy because of toxicity (4 pts) or personal reasons (1pt). Median duration of ongoing subsequent treatment is 8 months (range 1.7–25). The survival rate after a median follow-up of 3.9 months since failure to frontline therapy is 87%. Conclusion: Failure after frontline therapy with second generation TKI is an uncommon event, most frequently associated with toxicity or patient preference. Most of these patients respond well to alternative TKI. This adequate response should alleviate the fear of not having available effective therapy if patients fail to respond to 2nd generation TKI when used as frontline therapy. Disclosures: Kantarjian: BMS: Research Funding; NOVARTIS: Research Funding. Cortes:BMS: Research Funding; NOVARTIS: Research Funding; Pfizer: Consultancy, Research Funding.

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Outcomes of Patients with Refractory/Relapsed Diffuse Large B-Cell Lymphoma Who Progress After Autologous Stem Cell Transplantation in the Rituximab Era.

Blood ◽

10.1182/blood.v120.21.2689.2689 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2689-2689

Author(s):

Sarah J. Nagle ◽

Kaitlin Woo ◽

Rosemarie Mick ◽

Stephen J. Schuster ◽

Sunita D. Nasta ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cell Transplant ◽

First Line ◽

Large B Cell Lymphoma ◽

Historical Controls ◽

First Line Treatment

Abstract Abstract 2689 Salvage chemotherapy and autologous stem cell transplant (ASCT) remain the current standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who have primary refractory disease or relapse after initial therapy. The addition of rituximab results in improved overall survival (OS) after first line treatment, but cure rates of salvage therapy and ASCT are inferior when compared to historical controls (Gisselbrecht et al, JCO 2010). In the pre-rituximab era, patients with DLBCL who progressed after ASCT had an extremely poor prognosis, with a median OS of 3 months from the time of progression (Vose et al, Blood 1992). There is a paucity of data regarding outcomes and clinical patterns following progression after ASCT in the rituximab era. We conducted a retrospective analysis using our institutional database of DLBCL patients who underwent ASCT for primary refractory or relapsed disease. For those who progressed after ASCT, we evaluated OS defined as time from date of progression after ASCT to date of death from any cause or last follow-up. We also analyzed OS for various subgroups based on their clinical characteristics and post-progression therapy. The impact of post-progression therapy on outcome was assessed by calculating OS from the time of exposure to a particular treatment to date of death from any cause or last follow-up. Median OS was estimated by the Kaplan-Meier method and subgroup comparisons were performed using the log rank test. We identified 215 patients with primary refractory or relapsed DLBCL who underwent ASCT between January 1, 2005 and December 31, 2011. All patients received rituximab as part of their first line treatment. Fifty-six patients (26% of total) were found to have progression after ASCT. Eight patients were excluded from the analysis because they were not re-biopsied at relapse (n=5) or they had indolent disease at relapse (n=3). Data on the remaining 48 patients (median age 57 years; range 20–74) were further analyzed. The median OS from progression after ASCT for the entire cohort was 10.7 months (95% CI: 6.8–18.0 months). Patients who progressed < 1 year from ASCT (n=39) had a significantly shorter OS than those who progressed ≥ 1 year from ASCT (n=9): 9.5 vs. 26.7 months (p=0.02). Patients with at least stable disease as first assessment after ASCT (n=29) had a significantly longer OS than those who progressed immediately after ASCT (n=19): 18 vs. 6 months (p=0.01). Patients who were exposed to at least one novel agent (lenalidomide, radioimmunotherapy, non-rituximab monoclonal antibodies or tyrosine kinase inhibitors) as part of their post-progression therapy after ASCT (n=20) had a median OS of 11.2 months from treatment initiation. In contrast, patients who were treated with conventional cytotoxic chemotherapy but not novel agents (n=20) had a median OS of 6.7 months. In particular, patients who underwent radioimmunotherapy at some point after progression post-ASCT (n=9) had a median OS of 17.5 months (95% CI: 2.6-n/a months) with one patient in complete response > 48 months after the treatment. Patients who underwent allogeneic stem cell transplant following progression after ASCT (n=6) had a median OS of only 7.1 months (95% CI: 0.8-n/a months). In the rituximab era, the median OS of DLBCL patients who progress after ASCT appears improved when compared to historical controls, especially in those who progress > 1 year from ASCT. Patients with DLBCL progressing after ASCT should be considered for therapy with novel agents, which may result in long term survival. 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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Long Term Molecular Remissions after Autologous Haematopoietic Stem Cell Transplant in Follicular Lymphoma.

Blood ◽

10.1182/blood.v112.11.2185.2185 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2185-2185

Author(s):

Séverine Lissandre ◽

Patrick Vourch ◽

Isabelle Desbois ◽

Lotfi Benboubker ◽

Caroline Dartigeas ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Progression Free Survival ◽

Haematopoietic Stem Cell ◽

Cell Transplant ◽

First Line ◽

Molecular Remission ◽

Remission Duration

Abstract Background and aim of the study: Autologous stem cell transplant (ASCT) has been shown to be an effective treatment for first-line and relapsed follicular lymphomas (FL). But no long term molecular remission was described. The aim of this retrospective study was to determine the clinical and molecular outcome of patients with FL who received ASCT during a 12-year period. Method: All patients who underwent ASCT for first-line or relapsed FL between January 1992 and December 2004 were included. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method and cumulative incidence of nonrelapse mortality (NRM), with relapse as a competing event, by Fine and Gray method. Patient characteristics: Seventy-one patients with a median age of 45 years and a median follow-up of 108 months were analysed. The majority were of the subtype grade 1 (57 %), had a high tumour burden (50 %) and were treated in firstline (52 %). After an anthracyclin-based induction regimen, 12 patients were in first complete remission (CR), 25 in first very good partial response (VGPR), 8 in second CR and 26 in second VGPR. They received BCNU, Etoposide, Aracytine, Melphalan (BEAM in 58 %) or Cyclophosphamide, total body irradiation (42 %) as conditioning for the ASCT. The majority of them received an unpurged graft (58%). Results : Thirty-eight patients were alive, 24 without progression between 4 and 12 years; 31 patients had died, 7 without progression. A total of 38 patients (55 %) developed recurrent lymphoma. Median OS was estimated at 8 years and 4 months. The ten-year PFS and the ten-year OS were 33 % and 47 %, respectively and the tenyear molecular PFS was 37 %. There was an apparent plateau on the remission duration curve at 32 % at 72 months and on the molecular remission duration curve at 37 % at 80 months. A plateau on the OS curve seemed to emerge at 41 % from the tenth year. Patients who received a purged graft had better OS and better PFS (median OS not reached versus 50 months, p = 0.08; median PFS not reached versus 22 months, p = 0.035) Three patients developed a secondary neoplasm and two a secondary myelodysplastic syndrome. The 10-year non-relapse mortality (NRM) was 20 %. Conclusion : This long follow-up study showed a plateau on the PFS and on the molecular PFS curves, suggesting that a selected group of patients might be cured by ASCT.

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Outcomes of HMA and Venetoclax in Relapsed AML Post-Allogenic Hematopoietic Stem Cell Transplant

Blood ◽

10.1182/blood-2020-141715 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 33-34

Author(s):

Osama Diab ◽

Haitham Abdelhakim ◽

Joseph P. McGuirk ◽

Tara Lin

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Complete Remission ◽

Hematopoietic Stem Cell ◽

Research Funding ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Pharmaceutical Research ◽

Cell Transplant ◽

Hematopoietic Stem

Background: There is no standard of care treatment for Acute Myeloid Leukemia (AML) in relapse post-allogeneic hematopoietic stem cell transplant (post-HSCT), with overall 5-year survival about 5-10%. Venetoclax (Ven) is a novel BCL2 inhibitor approved by the FDA for treatment of newly diagnosed AML in combination with hypomethylating agents (HMA) or low dose cytarabine for patients unfit for intensive induction. However, data in relapsed/refractory AML are limited, especially in the post-HSCT setting. In this retrospective study, we reviewed outcomes of patients with AML relapse post-HSCT who received Ven in combination with HMA in a single center. Methods: Charts of 17 patients who had AML relapse post-HSCT treated with combination of Ven and HMA between November 2018 - March 2020 at the University of Kansas Medical Center were reviewed. We utilized descriptive statistics for baseline characteristics and outcomes, and Kaplan-Meier log-rank test for calculating overall survival. Results Seventeen patients received Ven+HMA for AML relapse post-HSCT in our center. At the time of SCT, patients were in first complete remission (CR) (n=15); second CR (n=1) and primary failure induction (1). Median age was 62 at time of relapse (31-71) years, and 8 patients were female (47%). 9 patients (53%) had adverse risk AML (ELN 2017) 8 of them were in CR1 and 1 with primary induction failure. Common mutations included DNMT3a, ASLX-1, TET2 (3); TP53 (2); IDH1/2 (2); NPM1/FLT3 (1); NPM1/IDH2 (1); NPM1 (1 transplanted in CR2); FLT3 (1). 2/17 had received Ven+HMA prior to SCT; 4 patients received HMA alone prior to SCT. 11 patients (65%) were naïve to either Ven or HMA prior to relapse. Median time to relapse was 181 (44-851) days post-HSCT. 9 (53%) patients received Azacitidine+Ven and 8 (47%) received Decitabine+Ven. HMA+Ven was the first line of therapy post-HSCT relapse in 14 patients. 2 had donor lymphocyte infusion (DLI) after either MEC or dacogen but relapsed prior to Ven+HMA. 1 had IDH (2) inhibitor. Patients received median of 2 (1-10) cycles of HMA+Ven. Six (35%) patients achieved complete remission/complete remission with incomplete hematologic recovery (CR/CRi), and 2/6 patients had negative measurable residual disease by multiparameter flow cytometry. Median overall survival was 361 days from relapse (Figure 1). 3/14 patients received subsequent DLI with Ven+HMA. Disease progression was the most common cause of death in 8/9 of patients who died during the follow up period. Most common side effects included neutropenic fever (n=8, 47%) and acute graft versus host disease (aGVHD) (n=5, 30%). 2/5 developed new aGVHD on HMA+Ven with no prior history of aGVHD. However, aGVHD was mainly grade I-II and responsive to therapy. Discussion HMA+Venetoclax demonstrates potential activity in patients with AML relapse post-HSCT with a CR/CRi rate of 35%, comparable to other salvage therapies. There were no unexpected side effect in this high-risk population. Larger studies are needed to confirm efficacy and toxicity in this setting. Disclosures McGuirk: Pluristem Ltd: Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Bellicum Pharmaceutical: Research Funding; Allo Vir: Consultancy, Honoraria, Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Astellas: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding. Lin:Aptevo: Research Funding; Abbvie: Research Funding; Bio-Path Holdings: Research Funding; Celgene: Research Funding; Gilead Sciences: Research Funding; Incyte: Research Funding; Jazz: Research Funding; Mateon Therapeutics: Research Funding; Ono Pharmaceutical: Research Funding; Pfizer: Research Funding; Prescient Therapeutics: Research Funding; Seattle Genetics: Research Funding; Tolero Pharmaceuticals: Research Funding; Trovagene: Research Funding; Genetech-Roche: Research Funding; Celyad: Research Funding; Astellas Pharma: Research Funding.

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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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Rituximab Plus Hypercvad (R-HCVAD) Alternating with Rituximab Plus High-Dose Methotrexate-Cytarabine (R-M/A) in Untreated Mantle Cell Lymphoma (MCL): Prolonged Follow-Up Confirms High Rates of Failure-Free Survival (FFS) and Overall Survival (OS).

Blood ◽

10.1182/blood.v104.11.128.128 ◽

2004 ◽

Vol 104 (11) ◽

pp. 128-128 ◽

Cited By ~ 5

Author(s):

Jorge Enrique Romaguera ◽

Luis Fayad ◽

Maria A. Rodriguez ◽

Fredrick B. Hagemeister ◽

Barbara Pro ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Complete Remission ◽

Stem Cell Transplant ◽

Pulmonary Hemorrhage ◽

Myelogenous Leukemia ◽

High Dose ◽

Hematologic Toxicity ◽

Cell Transplant

Abstract Introduction: Aggressive MCL has a poor prognosis with a 21-40% complete remission (CR) after CHOP and a duration of response of only 10-16 months. More intense therapy could improve these statistics. Rituximab is effective in MCL and has minimal toxicity. Methods: A prospective phase II trial of R-HCVAD (considered to be one cycle) alternating every 21 days with R- M/A (considered to be another cycle) as described earlier (Ann Oncol. 13, suppl 2, 2002 #24). Prophylaxis with mesna, calcium leucovorin, prednisone eyedrops, G-CSF, antibacterial, antifungal, and antiviral therapy. CBC with differential and platelet counts X 2-3/week. Re-staging every 2 cycles including upper and lower endoscopies. Patients in complete remission (CR) after 6 courses of a planned 6-8 cycles were not offered consolidation with stem cell transplant. Post-treatment evaluation was performed every 3 months for 1 yr, every 4 months for 2 yrs, every 6 months for 2 years, then annually. Results: Of 100 patients registered, one was ineligible and two decided to not receive the treatment after registration, leaving 97 evaluable for analysis of response, survival and toxicity. An analysis of response after the first 6 cycles shows an 87% CR/CRu rate. With a median follow up of 40 months, the 3-year FFS and overall survival (OS) were 67% and 81%, respectively. Adverse factors for FFS were: Grade 4 hematologic toxicity was significant. Five patients died during treatment of sepsis (3), pulmonary hemorrhage (1), and unknown cause (1). Four patients developed myelodysplasia/acute myelogenous leukemia after treatment and while in CR and three have died, for a total of 8 deaths in the study (8%). Conclusion: R-HCVAD alternating with R-M/A without stem cell transplant is an effective regimen for treatment of aggressive untreated MCL, specially for patients ≤ 65 years old. Toxicity is as expected for an intense regimen. This encouraging data warrants continued follow-up and comparison with existing/new therapies in future trials.

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