The Role of Total Body Irradiation (TBI) in the High-Dose Regimen of Patients with Follicular Lymphoma (FL) Treated with Autologous Stem Cell Transplant (ASCT) in the Rituximab Era. A Retrospective Study of the EBMT Lymphoma Working Party

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 502-502
Author(s):  
Inas El-Najjar ◽  
Ariane Boumendil ◽  
Jian Jian Luan ◽  
Catherine Thieblemont ◽  
Didier Blaise ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Dose Regimen ◽  
Research Funding ◽  
High Dose ◽  
Cell Transplant ◽  
Data Set ◽  
High Dose Regimen

Abstract Abstract 502 Background and Aims: Rituximab has become an essential component of FL treatment, either in combination with chemotherapy or as maintenance. However, there is not much data available regarding the influence of prior rituximab on the survival of patients after ASCT. In addition, there is no consensus regarding the best type of high-dose regimen. The aim of this study is to assess the outcome of patients with FL having ASCT according to the high-dose regimen and previous treatment with rituximab. Patients and Methods: Between 1995 and 2007, 7910 patients with FL had their 1st ASCT and were reported to the EBMT registry. A full data set was available for 2233 patients who had ASCT with either TBI containing regimens or BEAM, and constitute the study group. Overall survival (OS) and event-free survival (EFS) were determined using the Kaplan-Meier method, and curves were compared by log-rank test. In multivariate analysis, the relevance of prognostic factors was estimated using Cox regression model. Incidence of relapse (IR) and non-relapse mortality (NRM) were calculated by cumulative incidence curves compared by Gray's test. Multivariate analysis of IR and NRM used Fine and Gray model. Results: Six hundred and eighty patients received a TBI-containing regimen, and 1553 patients BEAM. Seven hundred and thirteen patients (32%) had been treated with monoclonal antibodies (MoAb) before ASCT (confirmed as rituximab in 665). Patients who had TBI were younger (median age: 47) than patients who underwent BEAM (median age: 49; p<0.001), and were transplanted in 1st remission more frequently (61%) than BEAM patients (44%, p<0.001). In contrast, more patients treated with BEAM had received MoAb prior to ASCT (37%) than TBI patients (21%, p<0.001). Peripheral blood was the source of stem cells in 98% of patients having BEAM in comparison with 92% of patients having TBI (p<0.001). After a median follow-up of 60 months, the median overall survival (OS) for the whole group was 146 months and the median EFS, 72 months. Multivariate models for analysis of prognostic value of TBI were all adjusted on disease status at transplant, age, previous MoAb, time from diagnosis to ASCT, and source of stem cell and significant risk factors are shown in the table. In addition there was a trend for patients receiving TBI to have a better OS than patients receiving BEAM (p=0.06). Moreover, females had better EFS (p = 0.011) and OS (p = 0.058) in univariate analysis. However, the gender survival curves did not fulfil the proportional hazards assumption and thus the multivariate analysis of OS and EFS were stratified on gender allowing no estimation of its effect on outcome. Conclusions: In contrast to observations made in patients autografted before 1995 (Montoto Leukemia 2007), in the present series (with a shorter follow-up) the beneficial effect of TBI over BEAM in terms of relapse prevention was not counteracted by an increased NRM, resulting in a significantly better EFS with TBI in the rituximab era. Unlike reported for aggressive lymphoma, use of MoAb (rituximab) prior to ASCT had no detrimental impact on outcome and in fact was associated with significantly better OS. The superior survival of female patients in the rituximab era needs to be confirmed in further studies. Disclosures: Blaise: Laboratoire Pierre Fabre: Research Funding; Celgene: Research Funding. Rambaldi:Italfarmaco S.p.A.: Consultancy, Honoraria. Gribben:Roche: Honoraria; Celgene: Honoraria; GSK: Honoraria; Mundipharma: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria. Montoto:Genentech: Research Funding; Roche: Honoraria.

Autologous Stem Cell Transplantation (autoSCT) for HIV-Associated Lymphoma in the Era of Combination Antiretroviral Therapy (cART): A Retrospective Analysis of the EBMT Lymphoma Working Party

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2257-2257 ◽  
Author(s):  
Kai Huebel ◽  
Alessandro Re ◽  
Ariane Boumendil ◽  
Herve Finel ◽  
Marcus Hentrich ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Dose Regimen ◽  
Research Funding ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Hiv Patients ◽  
High Dose Regimen

Abstract Introduction: Patients infected with HIV have an increased risk of developing aggressive B-cell non-Hodgkin lymphoma and Hodgkin lymphoma (HL). The continuous development of cART during the last decade has improved the prognosis of HIV-associated lymphoma considerably. However, a significant proportion of these patients will experience lymphoma relapse and may be candidates for autoSCT. The purpose of the present study was to investigate if recent advances in anti-lymphoma therapy and anti-infectious strategies have influenced the outcome of autoSCT for HIV-related lymphoma. Patients and methods: For this retrospective study, all EBMT-registered patients aged 18 years or older with HIV-positive serostatus who were treated with a first autoSCT between 2007 and 2013 were eligible. Baseline patient, disease, and transplant data were collected from MED-A forms. Centers were requested to provide additional HIV and lymphoma treatment and follow-up information. Statistical analysis used log rank test to assess the impact of baseline characteristics on survival endpoints. In multivariate analysis, the relevance of prognostic factors was estimated using Cox regression models. Curves of cumulative incidence of relapse (IR) and non-relapse mortality (NRM) were compared by Gray's test. Results: 138 patients from 25 European centers met the eligibility criteria and had the full data set required for this analysis available. 86% were male, median age was 44 years (range 24-69). Underlying diagnoses were diffuse large B cell lymphoma (DLBCL) in 46%, HL in 21%, Burkitt lymphoma in 14%, plasmablastic lymphoma (PBL) in 10%, and other lymphoma in 9% of the patients. Disease status at autoSCT was complete remission (CR) in 51%, partial remission (PR) in 33%, and less than PR in 16% of the patients, achieved after 1 (28%), 2 (58%), or more than 2 lines of chemotherapy (14%). With HIV load below the threshold of detection in 74% of the patients, the median CD4+ cell count was 187/µl (range 0-800) at transplant. 95% of the patients continued with cART during salvage and high-dose chemotherapy. BEAM was used as high-dose regimen in 77% of the patients. With a median follow-up of 4 years, 2-year NRM, IR, progression-free survival (PFS) and overall survival for the whole series were 9%, 23%, 68% and 70%, respectively. By multivariate analysis, diagnosis DLBCL or PBL (vs HL), increasing number of chemotherapy pretreatment lines, and less than PR at autoSCT were significant predictors of an unfavorable PFS; whilst age, high-dose regimen, performance status, and viral load had no significant impact. 2-year PFS in patients with 1st-line CR, later CR, PR, or less than PR at autoSCT was 91%, 80%, 64%, and 23%, respectively. Conclusions: This series, which is the largest ever on lymphoma transplants in HIV+ patients, suggests that in the cART / chemoimmunotherapy era, the outcome of autoSCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of HIV infection. AutoSCT under ongoing cART therapy remains the treatment of choice for HIV+ patients with PBL or recurrent DLBCL or HL. Disclosures Kröger: Sanofi: Honoraria, Research Funding; Neovii: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Montoto:Roche: Honoraria; Gilead: Research Funding. Dreger:Novartis: Consultancy; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Gilead: Consultancy; Janssen: Consultancy; Roche: Consultancy.

scholarly journals Similar Survival with Deferred Versus Salvage Autologous Stem Cell Transplant in Light Chain Amyloidosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4579-4579 ◽  
Author(s):  
Danny Luan ◽  
Koen Van Besien ◽  
Paul J Christos ◽  
Roger Pearse ◽  
Danielle Guarneri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Light Chain ◽  
Research Funding ◽  
Small Sample ◽  
Renal Amyloidosis ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant

Background: Light chain (AL) amyloidosis is characterized by deposition of misfolded monoclonal immunoglobulin light chains leading to organ dysfunction. AL amyloidosis has traditionally been treated with agents used in multiple myeloma, primarily alkylators, proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), and high-dose melphalan/autologous stem cell transplantation (ASCT). A retrospective study comparing patients with AL amyloidosis who underwent ASCT as frontline therapy ('upfront ASCT') to those undergoing ASCT following induction ('deferred ASCT') revealed that deferred ASCT was associated with prolonged overall survival (OS) compared to upfront ASCT (Afrough et al, Biol Blood Marrow Transplant, 2018). Given the number of effective new therapies for AL amyloidosis, the potential to delay ASCT after one or more lines of therapy ('salvage ASCT') is feasible. To our knowledge, transplant outcomes of AL amyloidosis patients undergoing deferred vs salvage ASCT following at least one relapse have not been reported. A retrospective chart review was conducted to compare AL amyloidosis patients receiving deferred vs salvage ASCT for progression-free survival (PFS) and overall survival (OS). The study was approved by the Institutional Review Board at Weill Cornell Medical College. Methods: Twenty-four patients with AL amyloidosis who underwent deferred or salvage ASCT between 2000-2018 were included in the analysis. Patients who underwent upfront ASCT without induction chemotherapy were excluded. Demographics and clinical parameters were extracted from the electronic medical record. PFS was calculated from date of ASCT to first relapse and OS was calculated both from date of diagnosis and date of ASCT to death. Patients were censored if lost to follow-up prior to experiencing the relevant event. PFS as well as OS of patients who underwent deferred vs salvage ASCT were compared. Log-rank tests were used to statistically evaluate differences between Kaplan-Meier PFS/OS curves. Cox proportional hazards models were used to calculate hazard ratios (HR) using deferred ASCT as the reference treatment. Results: Among the 24 patients included in this analysis, 13 underwent deferred ASCT with 1 prior line of chemotherapy (e.g., induction), and 11 underwent salvage ASCT with a median of 3 prior lines (Table 1). Ten patients had cardiac amyloidosis, 15 had renal amyloidosis, and 6 had multi-organ involvement. Induction regimens received in the deferred group are included in Table 1. Neither PFS nor OS was significantly different between patients receiving deferred vs salvage ASCT. After median follow-up of 2.9 years, median PFS in patients who received deferred ASCT was 6.5 years and not reached in those who received salvage ASCT (P=0.47), with a HR of 1.74 (95% CI, 0.38-7.85) (Figure 1A). Median OS from date of ASCT was not reached in either group after a median follow-up of 2.8 years (P=0.52), with a HR of 2.16 (95% CI, 0.19-24.04) (Figure 1B). Similarly, median OS calculated from date of diagnosis was not significantly different between deferred vs salvage ASCT (P=0.79) (Figure 1C). Conclusions: In this cohort of 24 AL amyloidosis patients, no significant differences in PFS or OS were seen between patients undergoing deferred ASCT following induction vs salvage ASCT following multiple lines of therapy. Unlike the superior OS seen with deferred vs upfront ASCT, our findings show that either deferred or salvage ASCT may be associated with comparable outcomes and suggest similar OS despite timing of transplant. However, it is important to note the small sample size and that none of our patients received daratumumab-based regimens which may have improved PFS/OS in either or both groups. There were also small differences between groups in use of maintenance (1 vs 3 patients in the deferred and salvage groups, respectively) and proportion of patients receiving higher doses of melphalan 200mg/m2 vs 140 mg/m2 (69% vs 55% in deferred and salvage groups, respectively). Nevertheless, the lack of difference seen in PFS and OS between the two groups suggests that eventual hematologic relapse and organ progression with death occur at similar time intervals despite timing of ASCT. This speaks to the point that in newly diagnosed AL amyloidosis as well as later in the disease, achieving deep responses to prevent organ progression and death regardless of timing of ASCT remains an important treatment goal. Disclosures Van Besien: Miltenyi Biotec: Research Funding. Coleman:Kite Pharmaceuticals: Equity Ownership; Pharmacyclics: Speakers Bureau; Merck: Research Funding; Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding. Rosenbaum:Janssen: Research Funding; Honoraria Akcea: Other: Accordant Health.

Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity.

1988 ◽  
Vol 6 (9) ◽  
pp. 1491-1500 ◽  
Author(s):  
A E Chang ◽  
T Kinsella ◽  
E Glatstein ◽  
A R Baker ◽  
W F Sindelar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Dose Regimen ◽  
Soft Tissue Sarcomas ◽  
Disease Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Regimen ◽  
Disease Free

We have previously reported the results of a randomized trial that demonstrated the survival benefit of adjuvant chemotherapy in the treatment of patients with high-grade extremity sarcomas compared with no chemotherapy. This regimen included doxorubicin, cyclophosphamide, and methotrexate. This report updates and extends our experience. The median follow-up of this trial is now 7.1 years and reveals a 5-year disease-free survival of 75% and 54% for chemotherapy and no chemotherapy groups, respectively (two-sided P [P2] = .037). The 5-year overall survival for patients in this trial was 83% and 60% for the chemotherapy and no chemotherapy groups, respectively, with a trend towards improved survival in the chemotherapy arm (P2 = .124). Because of doxorubicin-induced cardiomyopathy we performed a subsequent randomized trial comparing this high-dose regimen to reduced cumulative doses of doxorubicin and cyclophosphamide without methotrexate. Eighty-eight patients were entered into this trial which has a median follow-up of 4.4 years. The 5-year disease-free and overall survival for patients treated with the reduced doses of chemotherapy was 72% and 75%, respectively, and was not significantly different from the high-dose regimen. No patients developed congestive heart failure on this study. We conclude that adjuvant chemotherapy improves disease-free survival in patients with extremity soft-tissue sarcomas. The overall survival advantage in patients receiving adjuvant chemotherapy in our initial randomized high-dose chemotherapy trial has diminished though it continues to favor the chemotherapy group. A reduced-dose chemotherapy regimen was found to be comparable to the high-dose regimen.

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

Blood ◽  
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.

scholarly journals Progressive Multifocal Leukoencephalopathy in Multiple Myeloma: A Single Institution Case Series

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4736-4736
Author(s):  
Alfredo De La Torre ◽  
Andrew Gao ◽  
Timo Krings ◽  
Donna E. Reece
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Research Funding ◽  
Jc Virus ◽  
Brain Mri ◽  
Brain Biopsy ◽  
High Dose ◽  
Cell Transplant

Abstract Introduction Progressive multifocal leukoencephalopathy (PML), caused by the John Cunningham (JC) virus, is an infection that requires immunosuppression for its manifestations and is fatal disease in many cases. (1) After asymptomatic primary infection, which occurs in childhood, the virus remains quiescent. (1,4) The classical clinical presentation is that of a subacute symptomatology that develops over weeks or months and consists of diverse sensorimotor abnormalities depending on the site of brain involvement. Approximately 22 cases of PML amongst patients with multiple myeloma (MM) have been reported in the literature between 1965 and April 2020. (5) Methods We performed a retrospective chart review of all myeloma patients who were treated at the Princess Margaret Cancer Center from 2010-2020 to identify cases of PML. Patient and disease characteristics, responses, and survival outcomes were collected from Myeloma and Stem Cell Transplant databases and electronic patient records under REB approval. Results We identified 3 cases of PML in MM patients at our center over the past 10 years, all of which occurred in patients receiving therapy containing an immunomodulatory derivative (IMID), i.e., thalidomide, lenalidomide or pomalidomide. Patient 1 A 52-year-old male with kappa light chain MM presented in 2009 on hemodialysis and received upfront bortezomib and dexamethasone followed by melphalan 200mg/m 2 and autologous stem cell transplantation (ASCT) in March 2010; maintenance with thalidomide was given until July 2011 when he presented to the ER with left-sided weakness, facial droop, and decreased strength. CT scan showed right-sided hypodensity in keeping with demyelination. PML was confirmed by MRI, lumbar puncture with positive PCR for JC virus, and a brain biopsy (Fig 1 A-C). He was treated with mirtazapine, and also developed status epilepticus controlled with phenytoin and phenobarbital. His myeloma treatment was never resumed after the diagnosis of PML due to concerns about viral reactivation. Approximately 3 years after PML diagnosis, his serum free kappa protein levels started to increase; he remained on hemodialysis but experienced no new myeloma-related organ damage and no myeloma treatment was offered. His last follow-up in clinic was in March 2019. However, he succumbed to S. pneumonia septicemia in July 2019. Case 2 A 68-year-old female with IgG kappa MM diagnosed in 2004 was treated with high-dose dexamethasone induction followed by melphalan 200mg/m 2 and ASCT and relapsed 2 years later. She commenced cyclophosphamide and prednisone until July 2011 when treatment was changed to lenalidomide and prednisone; subsequent progression in February 2014 was treated with pomalidomide/bortezomib/prednisone. In November 2014, we noticed worsening vision. Brain MRI showed hyperintensity in T2 in the occipital lobe. Her myeloma treatment was stopped and she received corticosteroids with no improvement. LP in January 2015 was positive for JC virus and the diagnosis of PML was made. She was managed with supportive measures. Her last clinic follow-up was in 2015 and the patient died from progression in September 2015. Case 3 A 52-year-old male with IgA lambda MM diagnosed in 2015 was treated with CYBOR-D induction followed by melphalan 200mg/m 2 and ASCT. He initially received lenalidomide maintenance which was changed to bortezomib due to toxicity. On progression in January of 2019 he was placed on a clinical trial of the anti-BCMA antibody drug conjugate belantamab mafodotin in combination with pomalidomide and dexamethasone on which he achieved a VGPR. In October 2020, he developed confusion and memory problems, as well as involuntary twitching. A brain MRI showed possible demyelination Two LPs were negative for JC virus, but a targeted brain biopsy confirmed the diagnosis of PML (Fig 1 D-F). His myeloma treatment was discontinued, and he was started on mirtazapine. At his most recent clinic visit in May 2021 his speech, memory and functional status had improved considerably and there were no signs of myeloma progression. Conclusion Our current series of PML in MM showcases the potential contribution of IMIDs and other novel agents--such as the newer monoclonal antibodies like belantamab mafotidin-- to the reactivation of JC virus and subsequent PML. Our series also demonstrates that neurologic improvement and longer survival can be observed with earlier management. Figure 1 Figure 1. Disclosures Reece: BMS: Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Millennium: Research Funding; GSK: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding.

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 ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 128-128 ◽  
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.

Salvage Autologous Hematpoeitic Stem Cell Transplants (AHSCT2) for Myeloma: Single Center Experience.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4591-4591
Author(s):  
Bishoy Faltas ◽  
Jane L. Liesveld ◽  
Michael Becker ◽  
Jainulabdeen J. Ifthikharuddin ◽  
Gordon L. Phillips
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Median Overall Survival ◽  
Progressive Disease ◽  
Conflicts Of Interest ◽  
High Dose ◽  
The Impact

Abstract Abstract 4591 Although the role of AHSCT1 is well established in multiple myeloma therapy, the role of the salvage (not “tandem”) AHSCT2 is less clear. However, most pts. undergo initial stem cell harvests with plans for eventual AHSCT2. To clarify the indications, the prognostic factors and the outcomes of AHSCT2 in relapsed myeloma, we analyzed our experience in 19 pts. (pts.) who underwent salvage AHSCT2 between the 1994–2008. Mean age at AHSCT1/2 was 54.58 (SD 7.96)/57.03 (SD 8.10) respectively; 15 (79.0%) were males. At the time of diagnosis, 7 (36.8%) pts. had ISS stage I, 6 (31.6%) stage II, 3(15.8%) stage III and in 3 (15.8%) the ISS stage could not be determined. Isotypes: IgG 11 (57.9%), IgA 4 (21.1%), 1 (5.3%) pt. had IgM and 3 (15.8%) had light chain myeloma. Cytogenetics were normal in 6 (31.6%), abnormal in 5 (26.3%) and unavailable for 8 (42.1%) pts. The most common therapy received prior to AHSCT1 was Vincristine/Adriamycin/Dexamethasone in 11 (57.9%) pts.; 7 pts. were exposed to novel agents. One pt. achieved complete response (CR), 15 (79.0%) pts. achieved partial response (PR) and 3 (15.8%) pts. had stable or progressive disease after receiving the initial treatment. All pts. proceeded to receive high dose therapy with Melphalan (MEL), 2 pts received fTBI in addition to MEL. Mean MEL dose was 190.00 mg/m2 (SD 23.01); 15 pts. received 200 mg/m2. All pts. received >2×10e6/kg of CD34+ cells in the first and second transplants. At D+100 after AHSCT1, responses were: 4 (21.1%) CR, 1 (5.3%) VGPR, 8 (42.1%) PR and 6 (31.6 %) with lesser responses. Therapy to prolong response or for salvage after AHSCT1 was given in all pts before AHSCT2, including Thalidomide in 6 (31.6%), Bortezomib in 4 (21.1%) and Lenalidomide in 2 (10.5) pts. Median time to progression after AHSCT1 was 318 days [95 % CI 110– 573]. Median interval between AHSCT1 and AHSCT2 was 896.74 days (SD: 698.34 days). At the time of AHSCT2, 4 (21.1%) were in PR, 15 (79.0%) had progressive disease. For AHSCT2, all pts. Received MEL, one pt. received MEL + Cytoxan and one pt. received MEL + Bortezomib. The median MEL dose/m2 was 175.56 (52.04).All pts. survived AHSCT2 to D+100, responses were as follows: 3 (15.8%) VGPR, 9 (47.4%) in PR; 7 (36.9) pts. had lesser responses. After AHSCT2, nine (47.4%) pts. had grade III toxicity and only one pt. had grade IV toxicity (avascular necrosis). Maintenance therapy after AHSCT2 included Bortezomib in 7 (36.8%) pts., Lenalidomide in 5 (26.3%) pts. and Thalidomide in 4 (21.1%) pts. After AHSCT2, the median overall survival (OS) was 658 days [95 % CI 326–1330] and progression free survival (PFS) after AHSCT2 was 237 days [95 % CI 121– 397] (Figure 1). OS probability at 6, 12, 24 months after AHSCT2 was 81.3, 75.0, 39.3 % respectively. For all pts., the median OS time (i.e. time from diagnosis to death or last follow-up) was 2187 days [95% CI 1413– 4126]. At the end of the follow up period, a total of 14 pts. had died. Causes of death were progression in 12 (63.2%) and sepsis in 2 pts. (10.5%). The number of previous lines of chemotherapy, interval between transplants, disease status at the time of AHSCT1/2, type of myeloma and MEL dose were not predictive of OS and PFS. In the multivariate analysis, only age by decade at AHSCT2 and male gender were independent predictors of OS after AHSCT2 (HR 4.037, P= 0.01), (HR 3.74, P=0.07) respectively. Similarly, in the multivariate analysis for PFS after AHSCT2, age at AHSCT2 was an unfavorable independent predictor (HR 3.48, P=0.009) whereas relapse free response more than 18 months after AHSCT1 was an independent favorable predictor (HR 0.198, P=0.007).Our results are consistent with the few studies examining the impact of salvage transplants for myeloma which report a median overall survival ranging from 20.7 to 38.1 months from the time of AHSCT2.We conclude that salvage AHSCT2 can positively impact PFS and OS but efforts to improve outcomes are mandatory.FigureSEQ Figure ≂,* ARABIC 1Figure. SEQ Figure ≂,* ARABIC 1 X-axis represents time from AHSCT2 in days. Y axis represents survival distribution. Blue line = OS, Red = PFS. Disclosures: No relevant conflicts of interest to declare.

Thalidomide Combined With High Dose Melphalan Improves Event Free and Overall Survival In Patients With Newly Diagnosed Multiple Myeloma: Extended Follow-Up Of The HOVON-50 Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3332-3332 ◽  
Author(s):  
Henk Lokhorst ◽  
Bronno van der Holt ◽  
Sonja Zweegman ◽  
Edo Vellenga ◽  
Sandra Croockewit ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Research Funding ◽  
Previous Analysis ◽  
Alpha Interferon ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Melphalan

Abstract Background The randomised, open-label, phase III trial HOVON-50 was designed to evaluate the effect of thalidomide during induction and maintenance in newly diagnosed multiple myeloma patients. The previous analysis showed that thalidomide improved the primary endpoint EFS, but had no impact on OS (Lokhorst et al; Blood 2010 115: 1113-1120). Method Patients with Salmon & Durie stage II or III, age 18-65 years inclusive, were randomly assigned to arm A: 3 cycles of VAD (Vincristine, Adriamycin, Dexamethasone) or to arm B, 3 cycles of TAD (Thalidomide 200 orally, days 1-28 instead of Vincristine) Thalidomide was given from day 1 until 2 weeks before the stem cell mobilization with CAD (Cyclophosphamide 1000 mg/m2 iv day 1)and G-CSF. After induction therapy patients received 1 or 2 courses of high dose Melphalan (HDM) 200 mg/m2 with autologous stem cell rescue followed by maintenance therapy with alpha-Interferon (Arm A) or Thalidomide 50 mg daily (arm B) until relapse or progression. Between November 27, 2001 and May 31, 2005, 556 patients were randomised of which 536 patients were eligible for evaluation. As of July 2013 the median follow up of the 201 patients still alive is 99 months, range 65 – 130 months. Results The best responses achieved on protocol after extended follow-up were improved and significantly higher in the patients randomized to thalidomide: ≥ PR 88% vs 80 % (p<0.01), at least VGPR 66 % vs 55% (p<0.01), CR 31% vs 24 % (p=0.04), respectively. Similar to the previous analysis thalidomide improved EFS (censored at allo-SCT) from median 22 months to 33 months,; HR = 0.63, 95% CI [0.51 - 0.78], p<0.001) and PFS from median 25 to 33 months (HR =0.70, 95% CI [0.58 - 0.84], p<0.001). After 5 years of randomization the overall OS curves diverged and thalidomide improved median OS from 65 to 75 months. 10 years from randomization 27 % of patients randomized to alpha-Interferon are still alive and 35% of patients randomized to Thalidomide. For OS multivariate analysis showed prognostic significance for the whole group of patients for LDH (HR=1.52, 95% CI [1.15-2.00], P= 0.004) and ISS (HR=1.31, 95% CI [1.11-1.53, P=0.001]. For the secondary endpoint OS the thalidomide arm was superior when adjusted for covariates in multivariate analysis (HR = 0.80, 95% CI [0.64 – 0.99], P=0.045). The incidence of second primary malignancies (SPM) was similar between the two arms, as well as the actuarial probability to get an SPM within 5 years from start of the therapy (5-6%) or 10 years (9-10%) Conclusion After long term follow-up thalidomide in induction and maintenance treatment and in combination with HDM improves the quality of response and achieves superior EFS and OS. No increased incidence of SPM was observed as compared to patients not receiving thalidomide. This trial was registered on www. Trialregister.nl as NTR238 and was supported by the Dutch Cancer Foundation. Disclosures: Lokhorst: Genmab A/S: Consultancy, Research Funding; Celgene: Honoraria; Johnson-Cilag: Honoraria; Mudipharma: Honoraria. Minnema:Janssen Cilag: Consultancy, Honoraria. Sonneveld:Janssen-Cilag: Honoraria; Celgene: Honoraria; Onyx: Honoraria; Janssen-Cilag: Research Funding; Millenium: Research Funding; Onyx: Research Funding; Celgene: Research Funding.

scholarly journals Outcome of Adult Patients with Philadelphia Negative B Cell Acute Lymphoblastic Leukemia after Frontline Therapy Failure

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3718-3718 ◽  
Author(s):  
Punit L Jain ◽  
Koji Sasaki ◽  
Hagop Kantarjian ◽  
Farhad Ravandi ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Response Duration ◽  
Complete Response ◽  
Cell Transplant ◽  
Overall Response ◽  
Frontline Therapy

Abstract Introduction: Intensive induction-consolidation chemotherapy achieves high rates of complete response (CR) in 90% of patients with newly diagnosed acute lymphoblastic leukemia (ALL). However, almost a half of the patients relapse and their outcome after frontline chemotherapy failure is essentially poor. Methods: We retrospectively reviewed 463 patients with newly diagnosed Philadelphia-negative ALL from June 2002 to February 2015 at our institution. Overall survival was defined as the time interval from the date of relapse to the date of death. Kaplan-Meier method was used for survival analysis. Results: Of the 463 patients, 155 (33%) relapsed. Data on salvage therapy and long term follow-up was available in 76 patients (17%). The median time to relapse was 15 months (range, 1-111 months). The median number of salvage regimens administered was 1 (range, 1-7). Overall, 76 patients received at least 1 salvage therapy. Thirty (39%) patients received at least 2 salvage regimens and 18 (24%) received 3 or more salvage regimens. Baseline patient characteristics are summarized in the table 1. Median follow-up after frontline therapy failure was 16 months. The median survival after relapse was 8.3 months with the 1- year and 2-year survival rates being 46 % and 28% respectively. Salvage 1 included augmented HCVAD [n=13; 7/13 responses (6 CR, 1 CRp) for a median of 6 months], asparaginase based therapies [n=6; 2/6 response (2 CR) for a median of 2 months], monoclonal antibodies (MAB), blinatumomab, inotuzumab ozogamicin [n=19; 11/19 responses (6 CR, 5 CRp) for a median of 7 months], HCVAD + anti-CD20 antibody [n=11; 8/11 responses (5 CR, 3 CRp) for a median of 6 months], Miscellaneous [n=22; 2/22 responses (2 CR)] and HCVAD [n=5; 1/5 response (1 CR) for 1 month]. The overall response rate to Salvage 1 was 41% (22 CR, 9 CRp) for a median of 6 months. Nineteen (25%) patients received subsequent allogeneic stem cell transplantation (ASCT); 11 of them are alive with a median of 2 years with 7 of them in CR. Thirty patients received a second salvage regimen; the most commonly used one consisted of MAB (blinatumomab; inotuzumomab ozogamicin) [n=8; 4/8 responses (2 CR, 2 CRp) for a median of 2.5 months]. The overall response rate to salvage 2 was 30% (6 CR, 3 CRp) for a median of 3 months. At the last follow-up, overall 23 patients remained alive, 9 of them in CR. Conclusions: Outcome of patients with Philadelphia-negative ALL post frontline therapies failure is poor with a median survival of only 8.3 months. Though some salvage therapies can induce remissions, response durations are limited. Stem cell transplant after remission offers a potential of long term cure. These patients should be referred to clinical trials. Table 1. Baseline characteristics and outcome of adults with relapsed B cell ALL (Ph -) who received salvage chemotherapy: N (%)/ Median [range] N= 76 Age (years) 36 (18-86) Age ³ 60 15 (20) Male 46 (61) PS 2-3 9 (12) WBC at diagnosis (x 109/L) 7.2 [1-602] CD20 positivity at diagnosis 24 (32) Cytogenetic Abnormality Diploid 22 (29) Hypodiploid 8 (11) Hyperdiploid 12 (16) t(4;11) 5 (7) Miscellaneous 28 (37) Type of Induction chemotherapy, No. (%) Augmented BFM 28 (37) HCVAD 21 (28) HCVAD + anti-CD20 antibody 27 (35) Overall response to frontline therapy CR 73 (96) CR without platelet count recovery 2 (3) Partial response 1 (1) Median response duration, (month) 15[1-63] Response duration <12 months 35 (46) Complete response to salvage chemotherapy S1 31/76 (41) S2 9/30 (30) S3 or more 3/18 (17) Allogeneic stem cell transplant 19 (25) Figure 1. Overall survival Figure 1. Overall survival Disclosures Cortes: Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BerGenBio AS: Research Funding; BMS: Consultancy, Research Funding; Teva: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Daver:ImmunoGen: Other: clinical trial, Research Funding. Konopleva:Novartis: Research Funding; AbbVie: Research Funding; Stemline: Research Funding; Calithera: Research Funding; Threshold: Research Funding.

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