The Use of Novel Agents In Patients with Multiple Myeloma Initially Treated with Allogeneic Stem Cell Transplantation Results In A Significant Prolongation of Post Relapse Survival.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4580-4580
Author(s):  
Christopher P. Venner ◽  
Heather Sutherland ◽  
John Shepherd ◽  
Yasser Abou Mourad ◽  
Michael J. Barnett ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Research Funding ◽  
Statistical Significance ◽  
Novel Agents ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Significant Prolongation ◽  
Significant Difference ◽  
Relapsed Disease

Abstract Abstract 4580 Background: The use of allogeneic hematopoietic stem cell transplant (alloHSCT) in the treatment of Multiple Myeloma (MM) remains controversial. Although there is hope that alloHSCT may result in a cure, relapse continues to be a significant problem. The morbidity associated with late complications of allogeneic transplantation further compounds the issues faced when addressing relapsed disease. The use of Novel Agents (NA) in this patient population has been poorly characterized. Here we present our experience of NA use in patients initially treated with alloHSCT. Patients: 108 patients underwent an allografting procedure for their MM at our center between 1989 and 2009. 84 received a fully myeloablative procedure (15 received donor lymphocyte infusion). 24 received an autologous HSCT followed by a reduced intensity allogeneic procedure. 56 have relapsed with this population making up our primary cohort for analysis. 22 patients received NAs and very few patients received them prior to transplant (4/108). Endpoints examined were post relapse survival after the initial HSCT procedure (PRS), overall survival from time of initial treatment (OS) and progression free survival (PFS) measured in months (m). Results: Of the entire cohort of 108 patients median OS was 78.6m (95% CI; 24.5–132.6). Median PFS was 23.6m (95% CI; 15.4–31.8). Of the non-relapsed patients (n = 52) the median OS was 125.9m. In this cohort 67% of the deaths occurred within 1.5 years. Of the relapsed patients (n = 56) median PFS was 18.7m (95% CI; 14.6–22.8), median PRS was 31.5m (95% CI; 17.0–46.0), and median OS was 67.0m (95% CI; 31.6–102.5). The effect of NA was examined in the cohort of relapsed patients. No significant difference was noted in PFS between those exposed to NA and those who were not exposed (19.0m (95% CI; 10.1–22.8) vs 13.7m (95% CI; 5.8–21.6); p = 0.27). Exposure to NA showed improvements in PRS (42.3m (95% CI; 7.3–77.2) vs 10.4m (95% CI; 5.2–15.7); p = 0.01, Figure 1). A trend toward superior OS was noted (71.4m (95% CI; 37.9–105.5) vs 24.6m (95% CI; 3.0–46.1); p = 0.11) although this did not reach statistical significance. Conclusion: Ongoing management of relapsed patients with multiple myeloma in the post alloHSCT setting remains a significant challenge. This retrospective study demonstrates that the use of NA is both safe and effective in treating relapsed disease. The predominant impact of these drugs is seen in the relapsed setting. Exposure to NA correlates with a 22m improvement in PRS. A 46m improvement in OS is noted however, likely due to the small cohort, it failed to reach statistical significance. Disclosures: Sutherland: Celgene: Honoraria; Orthobiotech: Honoraria. Shepherd:Celgene: Honoraria; Orthobiotech: Honoraria. Nevill:Celgene: Honoraria. Toze:Hoffman La Roche: Consultancy, Honoraria, Research Funding; Genzyme: Honoraria, Research Funding; Glaxo Smith Kline: Honoraria.

scholarly journals Impact of Neurocognitive Dysfunction in a Veteran Population Undergoing First Outpatient Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5883-5883
Author(s):  
Shakira J. Grant ◽  
Lindsay M. Hannan ◽  
Jessica L. Brand ◽  
Robert E. Richard ◽  
Daniel Y. Wu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Cognitive Impairment ◽  
Daily Living ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
P Value ◽  
Cell Transplant ◽  
Neurocognitive Dysfunction ◽  
Hematopoietic Stem

INTRODUCTION Older adults (age > 70 years) with multiple myeloma (MM) are at higher risk of early mortality partly due to age-related factors, including impairments of cognition and function. To date, few studies have investigated the prevalence of neurocognitive impairment prior to autologous hematopoietic stem cell transplantation (ASCT) and its impact on post-transplant outcomes. We hypothesize, for patients with MM undergoing first outpatient ASCT, age >70 years or the presence of comorbid neurocognitive dysfunction decreases the time to first unplanned hospitalization occurring within 30 days post ASCT, and increases the overall length of stay (LOS) on the transplant service. METHODS We conducted a retrospective cohort study of 76 consecutive patients who underwent first ASCT at the Puget Sound Veterans Health Administration, for MM between January 2017 and December 2018. Patients with the following were excluded: amyloidosis, anaplastic plasmacytoma, and POEMS. Comprehensive psychological evaluations performed within 30 days prior to ASCT included: cognitive screening [Montreal Cognitive Assessment (MOCA)], depression [Patient Health Questionnaire-9 (PHQ-9)], and anxiety [General Anxiety Disorder- 7 (GAD-7)]. Functional status was assessed by activities of daily living (ADLS) and instrumental activities of daily living (IADLS). Data sources for table 1, included the institutional stem cell transplant database, and comprehensive electronic medical record review for each patient. This included vital status as of 7/15/19. Total LOS on the transplant service was measured as the time from arrival until discharge post-engraftment. For eligible patients, all portions of ASCT, including, stem cell collection, conditioning and stem cell infusion were completed as an outpatient. Statistical analyses were performed using SAS version 9.4. Kaplan Meier curves were generated to explore the association of cognitive scores and 1) time until first unplanned hospitalization within 30 days post-ASCT and 2) outpatient LOS on the stem cell transplant service. RESULTS Of the 76 patients undergoing ASCT, median age was 67 (range 40-79), 29% (22/76) were ≥ 70 years old . 67% (51/76) underwent ASCT within 1 year from diagnosis. The majority (73/76) scored ≥ 70 on a provider-assessed Karnofsky performance scale. Of those with MOCA scores available (n=64), impairments in cognition ranged from suspected mild cognitive impairment (MOCA 20-25) to probable cognitive impairment (MOCA 15-19), in 50% (32/64) and 6%( 8/64) of patients respectively. Those with MOCA scores< 26 were more likely to have ≥ 1 IADL impairment compared to those with scores ≥ 26 (Fisher Exact p=0.014). A total of 19 patients underwent planned hospitalization for conditioning followed by stem cell rescue, and therefore were not included in our analysis of unplanned hospitalization. Of the 57% (33/59) of patients with an unplanned inpatient admission within 30 days post-ASCT, the median time to first admission was 11 days. A total of 61% (17/28) and 53%(10/19) patients with MOCA <26 and ≥26, respectively, required hospitalization post-ASCT (log-rank p-value=0.70). There was no difference in the time to first unplanned hospitalization by age (<70, ≥70 years; log-rank p-value 0.58). Median time spent on the transplant service was 78 days (range 30 - 118). Suspected cognitive impairment did not influence time on the outpatient transplant service (median: 79 days MOCA <26 and 77 days MOCA ≥ 26, log-rank p-value=0.38). Median number of days on the transplant service differed by age group (log-rank p-value=0.02),) 76 vs 79 days in those age <70 and ≥70 respectively. CONCLUSION We found a high prevalence of cognitive impairment in MM patients undergoing first ASCT. However, we found no significant association between cognitive impairment or age and 30-day unplanned hospitalization. Older age (>70 years) was associated with a longer transplant service LOS. Thus, select older patients may have higher utilization of hospital resources post-ASCT compared to their younger counterparts. However confounding variables and selection bias may have influenced these preliminary results and additional analyses are ongoing. Future studies will evaluate the impact of age and pre-transplant neurocognitive function on additional outcomes, including longitudinal neurocognitive deterioration and impact on long-term morbidity and mortality. Disclosures Graf: TG Therapeutics: Research Funding; AstraZeneca: Research Funding; BeiGene: Research Funding.

Therapy Related MDS/AML In Multiple Myeloma Patients In The Era Of Novel Agents

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3117-3117
Author(s):  
Morie A Gertz ◽  
Suzanne R Hayman ◽  
David Dingli ◽  
Angela Dispenzieri ◽  
Prashant Kapoor ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
The United States ◽  
Lymphocytic Leukemia ◽  
Novel Agents ◽  
Cell Transplant ◽  
Trisomy 8 ◽  
To Receive

Introduction With the introduction of novel agents, survival in multiple myeloma has successively increased in the past decade. This improved survival increases the risk for late complications. Patients continue to receive melphalan therapy as a standard induction for those over the age of 65. Lenalidomide is considered a standard component of induction therapy in the United States for patients who are transplant candidates. Stem cell transplantation remains the standard of care for patients eligible to receive it. As a consequence of exposure to lenalidomide, stem cell transplant, and melphalan, the risk of late myelodysplasia and acute leukemia remains significant. We reviewed the Mayo Clinic experience with therapy-induced myelodysplasia beginning with the advent of novel agents. Patients and Methods All patients that carry the diagnosis of multiple myeloma between January 1, 2000, and September 1, 2011, were included. Patients with a synchronous diagnosis of a myeloproliferative or a myelodysplastic disorder or those who developed the myelodysplastic disorder within 15 months of first chemotherapy exposure were excluded. The date of diagnosis for the purpose of this abstract was based on first exposure to chemotherapy and not first detection of a monoclonal protein or smoldering multiple myeloma. All patients had to have morphologic verification in the bone marrow of dysplastic change consistent with therapy-related myelodysplasia. Results Of 3111 patients who had a myeloma diagnosis and first treatment after January 1, 2000, through September 1, 2011, 22 patients were identified to fulfill the criteria of myelodysplasia. There were 13 men and 9 women with a median age of 67 (46 to 82). At the time of this report, 17 have died. Prior to the development of myelodysplasia, exposure to an alkylating agent, lenalidomide, or an auto stem cell transplant was seen in 13, 15, and 10, respectively. Only one patient had been exposed to lenalidomide alone. Eighteen patients were classified as myelodysplasia. Four had acute non-lymphocytic leukemia. Metaphase cytogenetics was available in 19 and only one was normal. Twelve were hypodiploid. Trisomy 8 or abnormalities of chromosome 5 and 7 were present in 13. Seven patients received a hypomethylating agent with no clear evidence of response in any. Four patients had an allotransplant to manage the MDS/AML and only one survives 487 days after a matched-related donor allogeneic transplant. The median time from initial therapy of multiple myeloma to recognition of MDS or AML was 50.9 months (range: 15.2-146.5 months) fig 1. The median overall survival of the 22 patients is 6.5 months. Fig 2 Six of the 22 had active myeloma at the diagnosis of MDS/AML. Conclusion Myelodysplasia during the era of novel agents is a devastating complication of therapy with a very short survival and low response rate. As a time-dependent complication, the overall risk cannot be accurately estimated but has occurred in <1% of our patient population to date. Hypomethylating agents were ineffective in the seven that received it. One of four allotransplant patients remains alive. Ongoing surveillance for MDS/AML in this population is warranted and more effective therapies are needed. Disclosures: Kumar: Onyx: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

scholarly journals Treosulfan Conditioning for Allogeneic Transplantation in Multiple Myeloma Improved Overall Survival in Upfront Hematopoietic Stem Cell Transplantation — a Large Retrospective Study By the Chronic Malignancies Working Party of the EBMT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3464-3464
Author(s):  
Charlotte Gran ◽  
Junfeng Wang ◽  
Hareth Nahi ◽  
Linda Koster ◽  
Goesta Gahrton ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Relapse Rate ◽  
Research Funding ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Significant Difference

Abstract Background Allogeneic hematopoietic stem cell transplantation (AlloSCT) for treatment of multiple myeloma (MM) is controversial mainly due to high non-relapse mortality (NRM) with myeloablative conditioning. However, AlloSCT is probably the only treatment that result in cure of a small fraction of patients. Treosulfan is a prodrug of a bifunctional alkylating agent which has both myelotoxic and immunosuppressive properties. Conditioning regimes with treosulfan have been tried in various hematologic neoplasia such as AML and MDS indicating low NRM and increased progression free survival (PFS). Previous studies on use of treosulfan condition in AlloSCT for MM indicated feasibility, stable engraftment and low NRM. In the present study we have analysed the results of low and high dose treosulfan respectively on OS, RFS, relapse incidence and NRM as well as results of Treosulfan conditioning compared to non-Treosulfan reduced intensity conditioning (RIC) and non-Treosulfan myeloablative conditioning (MAC). Patients and Methods We conducted a retrospective analysis of 4544 patients with MM undergoing AlloSCT 2008-2016 reported to the EBMT data registry. Out of 537 patients receiving Treosulfan based conditioning the impact of dose could be analysed in 441. Three hundred and twenty-seven patients received a total dose of >36g/m2 and 114 <=36g/m2.These patients were compared to 2830 patients receiving RIC, and 1177 receiving MAC. 1103 patients were transplanted upfront and 3441 patients in later lines following relapse/progression. Patient characteristics shown in table 1. Results The 5-year OS in upfront Treosulfan conditioned patients was 62%, which was significantly superior to both non-Treo RIC and MAC patients respectively, apparently due to a tendency for lower NRM (10%) albeit a higher relapse rate (Table 2). Patients in later lines of conditioning had either low NRM (3rd line) or no significant difference (2nd line) (Table 2). Heterogeneity in the material makes it difficult to interpret results in the patients transplanted late in the course of the disease. A higher total treosulfan dose, >36g/m2, showed a tendency for improved OS and RFS compared to the lower dose treosulfan as well as RIC and MAC (table 2) respectively. In multivariate analysis of upfront transplanted patients, with a model adjusted for ISS score at diagnosis, age, Karnofsky score, response at AlloSCT, interval between diagnosis and transplant, donor type and donor - patient sex match, treosulfan and RIC retained significance for OS, HR 0.57 (P=0.006) and RFS, HR 0.65 (P=<0.005). For 2nd line Treosulfan RFS was significantly worse, HR 1.46 (P=<0.005) while there was no significant difference for OS between conditioning regimes in 2nd or for OS and RFS in 3rd line (table 2). The factors associated with most inferior OS in upfront line of conditioning was Karnofsky <90 and ISS score III at diagnosis. ISS score III at diagnosis was also associated with inferior OS also in 2nd and 3rd line (Table 2) A less then partial response at AlloSCT was consistently a factor associated with inferior RFS regardless of line of treatment with HR 1.67 (P=<0.005) in upfront, HR 1,63 (P=<0.005) in 2nd line and HR 1,66 (P=<0.005) for 3rd line or later (Table 2) In multivariate analysis of treosulfan based conditioning regimes, upfront line of conditioning was superior for OS, PFS and relapse as expected (Table 3). Notably was an increased hazard ratio for donor-patient sex match other than female to male in OS, PFS as well as relapse, HR 1.64 (P=0.02), HR 1.66 (P=0.004) and HR 1.83 (P=0.003) respectively (Table 3). Conclusions Conditioning upfront with Treosulfan containing regimens for AlloSCT in multiple myeloma, is associated with a superior overall survival and a low NRM, however with a slightly higher relapse rate compared to other regimens. A higher dose > 36g/m2 tends to further improve OS, RFS and relapse rate without increasing NRM. The better results of Treo conditioning in female to male transplants as compared to other sex combinations and in contrast to MAC transplants may be due to the overall lower NRM with treosulfan, thus utilizing the GVM more effectively as indicated by the trend for lower relapse rate. In conclusion, Treosulfan containing regimens appear to be of value in upfront AlloSCT. Prospective studies on Treosulfan conditioning are warranted to further define the best dosing in MM AlloSCT. Disclosures Niederwieser: Miltenyi: Speakers Bureau; Novartis: Research Funding. Beelen:Medac: Consultancy, Other: Travel Support. Stelljes:Pfizer: Consultancy, Honoraria, Research Funding; MSD: Consultancy; JAZZ: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Finke:Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding. Garderet:Amgen: Consultancy; Celgene: Consultancy; Takeda: Consultancy. Kroeger:Celgene: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; JAZZ: Honoraria; Novartis: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding.

scholarly journals A Retrospective Record Review of Mobilization Strategies with and without Plerixafor for Autologous Stem Cell Transplant in Patients with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5634-5634
Author(s):  
Tomer M Mark ◽  
Joseph S Bubalo ◽  
Gary Milkovich ◽  
Yvonne J Barnes ◽  
Edward Drea ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Safety Data ◽  
Disease Stage ◽  
Case Report Form ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Treatment Groups ◽  
Significant Difference ◽  
Transplantation Outcomes

Background: Autologous hematopoietic stem cell transplantation (ASCT) is the current standard of care in patients with multiple myeloma (MM) to support reconstitution of the bone marrow after myeloablative chemotherapy. Mobilization of blood progenitor cells to the peripheral circulation is stimulated via administration of granulocyte colony-stimulating factor (G-CSF) with or without chemotherapy. The addition of chemotherapy, typically cyclophosphamide, increases the yield of peripheral blood stem cells (also known as CD34+ cells) at the expense of additional toxicity. The unpredictability of harvest yield and the potential need for weekend apheresis sessions complicates mobilization planning when using chemotherapy. Plerixafor, a CXCR4 antagonist, in combination with G-CSF has been shown to be superior to G-CSF alone, leading to higher CD34+ yields in fewer apheresis sessions [Giralt et al, 2014]. However, the advantage of the combination of plerixafor with G-CSF is less well described in the context of new treatment options that can impair stem cell harvest yields when using G-CSF as the sole mobilization agent. Objective: The primary objective of this study was to determine clinical outcomes associated with G-CSF alone vs G-CSF + chemomobilization vs G-CSF + plerixafor from initiation of mobilization until 6 to 12 months after ASCT. Method: This is a retrospective study in patients with MM, carried out at 10 centers in the US. Patients were eligible if ≥ 18 years and undergoing first ASCT (≤ 12 months from initial diagnosis and no disease progression). Eligible patients were identified through a database query of hospital records of oncology patients diagnosed with MM and eligible for ASCT before June 2016. Patients fulfilling inclusion and exclusion criteria were attributed to three treatment arms depending on the mobilization regimen received:Arm 1: G-CSF + plerixaforArm 2: G-CSF + chemomobilizationArm 3: G-CSF Patients will be selected until 170 patients are assigned to each treatment arm or patient records are exhausted. Demographics, induction regimen, mobilization regimens and outcomes, apheresis, transplantation outcomes and survival status were extracted from medical charts and entered in the electronic case report form. Here, we present interim results from data collected at three centers as of June 24, 2019. Results: At the interim analysis cut-off date, 130 patients were included in the database (G-CSF: 52; G-CSF + plerixafor: 78; G-CSF + chemomobilization: 0). Demographic and baseline characteristics were comparable between the two treatment arms. More male patients were included (male: 63%, female: 37%) and the mean age was 58 and 59 years in the G-CSF and G-CSF + plerixafor groups, respectively (Table 1). Disease stage and the proportion of patients with poor-, intermediate- and high-cytogenetic risk status were similar in the two treatment groups. Few patients had a complete response (CR) after chemotherapy, but response rate (CR + partial response) was 91% in both treatment arms. The burden of apheresis in terms of number of sessions and blood volume processed was lower in patients receiving G-CSF + plerixafor compared with patients receiving G-CSF only (Table 2). CD34+ yield was higher in the G-CSF + plerixafor treatment arm, especially after the first apheresis session (Table 2). There was no difference in ASCT outcome between the two treatment groups. All patients had neutrophil engraftment except for one patient in the G-CSF only group, and all patients had platelet engraftment except one patient in each treatment group. There was no significant difference in the proportion of patients experiencing relapse between the two treatment groups at 6 and 12 months of follow-up. Overall, ≥ 90% of patients avoided relapse at 12 months. 96% and 93% of patients were still alive at 12 months in the G-CSF only and G-CSF + plerixafor treatment groups, respectively (Table 3). For the purpose of this study, safety data was not reviewed [Mozobil PI, 2019]. Conclusions: Per interim results, plerixafor reduced the burden of apheresis and increased CD34+ yields. Transplantation outcomes, relapse and overall survival at 6 and 12 months were not significantly different between the two treatment arms. Therefore, plerixafor could increase apheresis efficiency without compromising ASCT success in the context of currently used chemotherapy regimens. Disclosures Mark: Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Bubalo:Sanofi: Other: Research and writing support. Barnes:Sanofi: Employment. Drea:Sanofi-Genzyme: Employment. Fausel:Sanofi-Genzyme: Other: Grant to cover costs of data collection.

scholarly journals Characteristics, Outcomes and Treatment of Patients with T-Cell Prolymphocytic Leukemia (T-PLL) - Single-Center Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2997-2997 ◽  
Author(s):  
Etsuko Aoki ◽  
Preetesh Jain ◽  
Alessandra Ferrajoli ◽  
Zeev Estrov ◽  
Michael Keating ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Research Funding ◽  
Cell Transplant ◽  
Prolymphocytic Leukemia ◽  
Significant Difference ◽  
Frontline Therapy ◽  
Relapsed Disease

Abstract Background: T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive mature T-cell lymphoid leukemia. T-PLL is diagnosed based on characteristic immunophenotype, cytogenetic, and molecular aberrations (including members of the JAK-STAT signaling pathway) which may explain its aggressive clinical course. Cytogenetic features include chromosome (chr) 14 aberrations, accompanied by gene rearrangement involving proto-oncogenes TCL1 or MTCP1. In this analysis, we report our single-institution experience with T-PLL over the last 25 years. Methods: We reviewed the clinico-pathologic records of 101 consecutive patients (pts) with T-PLL, who presented to our institution between 1990 and 2015. The survival (OS) of pts was calculated from the date of initial presentation to the date of last follow up. Kaplan-Meier product limit method was used to estimate the median OS. Results: Median age of pts was 64 years (range 35-87 years). Eighteen pts (18%) presented with a performance status of 2 or higher. Lymphadenopathy, splenomegaly, skin lesions, hepatomegaly and pleural effusion were seen in 58%, 37%, 30%, 8%, and 7% of pts, respectively. Complex karyotype and aberrations in chr 14 were seen in 54 (63%) and 42 (49%) pts, respectively. TCL1 expression by immunohistochemistry was performed in 29 pts. The overexpression of TCL1 was detected in 23/29 pts (79%). Among untreated pts, 18/47 (38%) had a chr abnormality involving TCL-1. At initial presentation to our center, 59 pts (58%) were untreated and 42 pts (42%) had relapsed/refractory disease with a median of 2 prior treatments (range 1-6). Seventy-one pts (70%) were treated at our institution. Median overall OS from diagnosis in all pts was 21.7 mos (Range 1.5-107.7 mos). Median OS was longer in untreated pts than in pts with relapsed/refractory disease (27 mos vs. 17 mos; P=0.08). In a multivariate analysis for assessing the prognostic factors for OS in 43 untreated pts in whom all variables were available, we found that the presence of a pleural effusion HR (95% CI) 5.21 (1-27; P <0.04), high absolute lymphocyte count 1.009 (1.002-1.016; P = 0.006) and complex karyotype 4.6 (1.2-16.9; P = 0.02) predicted for increased risk of death. Fifty four evaluable pts (32 untreated and 22 with relapsed disease) received treatment with alemtuzumab based regimen, 36 as monotherapy and 18 in combination with pentostatin. Seventeen evaluable pts (1 untreated and 16 with relapsed disease) were treated with nelarabine. Overall response rate (ORR), complete remission rate (CR), median OS and progression free survival (PFS) are summarized in Table-1. Among 39 previously untreated pts who received treatment at our institution, the distribution of treatment regimen was alemtuzumab-based (n=32), nelarabine (n=1), other nucleoside analogues (n=5) and combination chemotherapy (n=1). Twenty two pts (56%) achieved complete remission (CR) after frontline treatment. Ten pts underwent allogeneic stem cell transplantation (SCT) after achieving a remission after initial treatment with alemtuzumab either as a monotherapy or in combination with pentostatin. We did not observe any significant difference in OS (Figure-1A) or PFS among pts who did/did not undergo stem cell transplantation after achieving an initial remission with the frontline therapies. Furthermore, we observed that there was no significant difference in OS among pts with or without a chr abnormality involving TCL-1 after frontline therapy (Figure-1B). Conclusions: In this retrospective analysis, we have observed that outcomes in T-PLL remain poor. We have shown that alemtuzumab has some therapeutic activity in pts with T-PLL but durable remissions are uncommon. Rarity of this disease limits the conduct of large scale clinical trials; hence multicenter collaborative effort is required to conduct prospective studies. In pts who achieve a CR, consolidation treatment with SCT did not improve survival in our series. Studies to further define the genomic imbalances in pts with T-PLL and identify potential therapeutic targets and pathways providing drug resistance in T-PLL are underway. Table 1 Summary of treatment response and outcomes according to the type of therapy *Censored at stem cell transplant. Table 1. Summary of treatment response and outcomes according to the type of therapy. / *Censored at stem cell transplant. Figure (A-B) - Survival of pts after treatment with frontline therapy A) with/without stem cell transplantation after initial remission. B) With/without TCL-1 rearrangements. Figure. (A-B) - Survival of pts after treatment with frontline therapy A) with/without stem cell transplantation after initial remission. B) With/without TCL-1 rearrangements. Disclosures O'Brien: Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Wierda:Acerta: Research Funding; Novartis: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Genentech: Research Funding. Jain:Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Novimmune: Consultancy, Honoraria; Abbvie: Research Funding; Servier: Consultancy, Honoraria; Seattle Genetics: Research Funding; Genentech: Research Funding; Celgene: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Infinity: Research Funding; Incyte: Research Funding; BMS: Research Funding. Thompson:Pharmacyclics: Consultancy, Honoraria. Kantarjian:BMS, Pfizer, Amgen, Novartis: Research Funding.

The Relationship of Response on Time to Next Treatment Based on Evidence from Two RCTs in Newly Diagnosed Stem Cell Transplantation Ineligible Multiple Myeloma Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2141-2141 ◽  
Author(s):  
Chrissy H. Y. Van Beurden-Tan ◽  
Hedwig Blommestein ◽  
Sonja Zweegman ◽  
Pieter Sonneveld
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Response Category ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Optimal Sequence ◽  
Significant Difference

Abstract INTRODUCTION The outcome of patients with Multiple Myeloma (MM) improved considerably over the last years due to an increase in availability of novel agents. However, the optimal sequence is largely unknown. Besides efficacy, determination of the optimal sequence is also of importance in light of cost effectiveness. To this end the development of a health economic (HE) model would be of interest. For such a model time to next treatment (TTNT) is required. We previously showed that in stem cell transplant (SCT) eligible patients TTNT was not treatment but response (i.e. complete, partial or no response; CR, PR or NR) dependent. We here investigate whether response was predictive for TTNT independent of the treatment regimen in SCT ineligible patients (pts) with MM. METHODS We analyzed patient level data of two phase 3 randomized controlled trials (RCTs) performed by the Dutch-Belgian cooperative HOVON group in newly diagnosed, transplant-ineligible patients. The HOVON-87 (N=668) compared Melphalan Prednisone (MP) with Thalidomide followed by Thalidomide maintenance (MPT-T) versus MP with Lenalidomide followed by Lenalidomide maintenance (MPR-R) (Zweegman et al Blood 2016) (EudraCT number 2007-004007-34). The HOVON-49 (N=333) compared MP versus MPT (including Thalidomide maintenance) (Wijermans et al J Clin Oncol 2010) (ISRCTN 90692740). The following data were included: treatment, best response, TTNT and survival status. Pts were censored after last date of contact. Pts who did not have information on TTNT and/or response were excluded from our analyses. Kaplan-Meier curves and Cox proportional hazards models were fitted on this data to investigate whether the TTNT is mainly response dependent and whether the quality of response is predictive for TTNT. RESULTS We included 519 HOVON-87 pts and 252 HOVON-49 pts. First, we analyzed the TTNT hazard ratios (HRs) of the active and comparative arm within each response category for both trials. The TTNT HR of the HOVON-87 pts with a CR (N=75) was not significantly different between treatments (HR 1.340, 95% CI: 0.590-3.039, p-val = 0.484). We also found no significant difference in PR pts (HR 0.952, 95% CI: 0.753-1.204, p-val = 0.681, N = 375) and NR pts (HR: 0.898, 95% CI: 0.518-1.556, p-val = 0.701, N=69). The number of CR pts in the HOVON-49 study was too low (N=8) to allow for a reliable analysis of this response category. Therefore, for this study we present very good PR (VGPR) as separate category. For both VGPR (N=44 pts) and PR pts (N=95 pts) we did see a significant difference in TTNT in the treatment arms (HR: 0.363, 95% CI: 0.174-0.757, p-val = 0.007 and HR:0.634, 95% CI: 0.417-0.965, p-val = 0.033 respectively). However, for NR pts the TTNT HR was similar (HR: 1.131, 95% CI: 0.746-1.714, p-val = 0.561, N=105 pts) Second, we compared the TTNT between the different response groups within each trial. For HOVON-87, the median TTNT for CR pts was 63.4 months (mos) (95% CI: 51.8 mos - not evaluable), for PR pts it was 24.6 mos (95% CI: 22.8 - 27.3 mos), and for NR pts it was 19.5 mos (95% CI: 9.7 - 25.3 mos). The TTNT of CR pts was significantly longer than of PR pts (HR: 3.923, 95% CI: 2.601-5.917, p-val = 0.000). And the TTNT of PR pts was significantly longer than of NR pts (HR: 1.411, 95% CI: 1.052-1.893, p-val - 0.000). For HOVON-49, the median TTNT for VGPR pts is 23.4 mos (95% CI: 15.0 - 26.7 mos), PR pts was 19.0 mos (95% CI: 15.4 - 21.5 mos), and for NR pts was 3.7 mos (95% CI: 3.4 - 4.3 mos). Only the TTNT of PR pts was significantly longer than the TTNT of NR pts (HR: 3.978, 95% CI: 2.938 - 5.388). CONCLUSIONS Data from the HOVON-87 showed a relationship between response and TTNT. Pts in this trial achieving a CR were observed to have a significantly longer TTNT compared to those achieving PR at best. Furthermore, TTNT was not significantly different for the treatment arms (e.g. patients with CR after MPR-R had similar TTNT than patients with CR after MPT-T). Establishing a relationship between response and TTNT was challenging among pts from the HOVON-49 since i) too few CR pts were seen in this trial and ii) the experimental arm included maintenance while the comparator treatment did not. We can conclude that the previous established relationship between response and TTNT was partly confirmed for newly diagnosed SCT ineligible MM pts. Further research is necessary to identify other relevant predictors for TTNT and to confirm the current findings before we can incorporate this into our HE model. Disclosures Blommestein: Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding. Zweegman:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding. Sonneveld:Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

scholarly journals Hematopoietic Stem Cell Transplant As Consolidation Treatment in Multiple Myeloma in Ecuador

2021 ◽  
Vol 27 (3) ◽  
pp. S444-S445
Author(s):  
Bella Maldonado-Guerrero ◽  
Mayhua Lam-Rodríguez ◽  
Julie Abifandi-Valverde ◽  
Migleth Cisneros-López ◽  
Ana Thur de Koos-Acosta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Consolidation Treatment

scholarly journals Tandem Autologous Hematopoietic Stem Cell Transplantation in Very Young Patients with Multiple Myeloma

2020 ◽  
Vol 09 (04) ◽  
pp. 233-235
Author(s):  
Rahul Naithani ◽  
Nitin Dayal ◽  
Reeta Rai
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Young Patients ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Platelet Recovery

Abstract Introduction Multiple myeloma (MM) in very young patients is uncommon, and no treatment guidelines exist for these patients. Patients and Methods We performed a retrospective analysis of five very young myeloma patients who underwent tandem autologous hematopoietic stem cell transplantation (HSCT). Results The median age was 37 years (range = 34–40 years). A median of two leukapheresis was performed (range = 1–4). The median number of hematopoietic stem cells collected was 5.4 × 106/kg (4.4–8.2 × 106/kg). During first transplant, four patients received melphalan of 200 mg/m2 and one patient received melphalan of 140 mg/m2 (due to renal failure) as conditioning regimen. Second transplant conditioning was melphalan of 200 mg/m2 for one patient and melphalan of 140 mg/m2 for remaining four patients. Two patients were in complete remission, and two were in very good partial remission and one patient progressed to active disease at the time of tandem autologous bone marrow transplant. All patients developed significant mucositis. Neutrophil and platelet recovery was longer in tandem autologous hematopoietic stem cell transplant. More viral infections were seen in tandem transplant. Day 30 and day 100 mortality was nil. Conclusion We present data on tandem autologous HSCTs in very young patients with MM in India. Responses continued to improve in this small series.

scholarly journals Long-term outcome after allogeneic stem cell transplantation in multiple myeloma

2021 ◽  
Author(s):  
Sini Luoma ◽  
Raija Silvennoinen ◽  
Auvo Rauhala ◽  
Riitta Niittyvuopio ◽  
Eeva Martelin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Outcome ◽  
Significant Difference ◽  
Relapse Group

AbstractThe role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma is controversial. We analyzed the results of 205 patients transplanted in one center during 2000–2017. Transplantation was performed on 75 patients without a previous autologous SCT (upfront-allo), on 74 as tandem transplant (auto-allo), and on 56 patients after relapse. Median overall survival (OS) was 9.9 years for upfront-allo, 11.2 years for auto-allo, and 3.9 years for the relapse group (p = 0.015). Progression-free survival (PFS) was 2.4, 2.4, and 0.9 years, respectively (p < 0.001). Non-relapse mortality at 5 years was 8% overall, with no significant difference between the groups. Post-relapse survival was 4.1 years for upfront-allo and auto-allo, and 2.6 years for the relapse group (p = 0.066). Survival of high-risk patients was reduced. In multivariate analysis, the auto-allo group had improved OS and chronic graft-versus-host disease was advantageous in terms of PFS, OS, and relapse incidence. Late relapses occurred in all groups. Allo-SCT resulted in long-term survival in a small subgroup of patients. Our results indicate that auto-allo-SCT is feasible and could be considered for younger patients in the upfront setting.

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