Addition Of Clarithromycin To Lenalidomide and Dexamethasone (BiRd) Is Effective In Multiple Myeloma After Progression On Lenalidomide and Dexamethasone

Abstract Background The combination of clarithromycin (biaxin), lenalidomide and dexamethasone (BiRd) has been previously shown by Niesvizky, R., et al as a very effective regimen in newly diagnosed myeloma (MM) with an overall response rate of 90.3% and a very good partial response (VGPR) rate of 73.6%. Long term follow up has shown a median progression free survival of 49 months. In a case control comparison, Gay, F., et al showed that BiRd has superior outcomes compared to lenalidomide and dexamethasone (Rd). Clarithromycin appears to optimize the pharmacologic effect of glucocorticoids by increasing the area under the curve and the maximum concentration levels of certain corticosteroids. Clarithromycin has immunomodulatory properties, partially mediated by the suppression of interleukin-6 and other inflammatory cytokines and may also have direct antineoplastic effects. Although the efficacy of BiRd in the frontline treatment of MM is well established, the effect of BiRd in patients who are refractory to Rd is unknown. Methods As part of an IRB-approved study we performed a retrospective analysis on all patients with MM in whom clarithromycin was added to Rd at the time of progression on Rd between January 2007 and March 2013. High risk MM was defined as having any one of the following: del(13q) by cytogenetics or t(4;14), t(14;16), t(14;20), -17p ,+1q21 on FISH/cytogenetics. International Staging System (ISS) stage was based on beta2 microglobulin and albumin at diagnosis of symptomatic myeloma. These data were available for 18 patients (75%). The definitions of progression, stable disease and response were as per the International Myeloma Working Group criteria. Event time distributions for overall (OS) and progression-free survival (PFS) were estimated with the method of Kaplan and Meier, and compared using the log-rank statistic, or the Cox proportional hazards regression model. Factors associated with BiRd response were selected based on cross tabulations and logistic regression modeling. Results 24 patients with MM who had disease progression on Rd had clarithromycin added to their regimen at the time of progression on Rd. Median age was 61 years (range: 41-80 years), 10 (41.6%) female, 11 (45.8%) had high risk features on cytogenetics or FISH, 6 (25%) had a prior stem cell transplant. All patients had shown evidence of disease progression on Rd prior to addition of clarithromycin. Median duration on Rd immediately prior to addition of clarithromycin was 5.2 months (range: 1.6-37.8 months). The regimen was well tolerated and only 2 patients needed a clarithromycin dose reduction. One patient developed dyspepsia, metallic taste, nausea and diarrhea. A second patient experienced grade 3 transaminitis. 10 patients, 41.6% (95% CI: 22.1, 63.4), achieved ≥PR. The clinical benefit rate (CR+VGPR+PR+MR) was 45.8% (95% CI: 25.6, 67.2). The median time to response was 4.4 months (range: 1-13.6 months) and the median duration of response was 17.3 months (range: 7.4-130.5 months). Median overall survival was 25 months with a median follow-up of 27.5 months. The median progression free survival (PFS) was 4 months. Age and prior therapy were significant risk factors for PFS. Patients over the age of 60 had a higher hazard of progression or death than patients under the age of 60 (HR 3.48 95% CI 1.09-11.09, p=0.04). The hazard of progression or death was increased by a factor of 1.59 for each additional prior therapy HR= 1.59 (95% CI: 1.19, 2.11), p=0.002. Patients initially responding to Rd (n=10) were more likely to respond to BiRd (n=6), 60% (95% CI: 26.2, 87.8) compared to patients that did not have an initial response to Rd (n=14) in whom the response to BiRD (n=4) was 28.6% (95% CI: 8.4, 58.1), OR=3.75, p=0.13. High risk genetics, prior stem cell transplant, and prior response to Rd did not correlate with PFS or response to BiRd, although the numbers are small. Conclusion Addition of clarithromycin to lenalidomide and dexamethasone (BiRd) can overcome resistance to lenalidomide and dexamethasone in a subset of patients and lead to clinical durable responses. This retrospective data may serve the basis for prospective evaluation of this effect. Disclosures: Off Label Use: Addition of clarithromycin to overcome resistance to lenalidomide and dexamethasone.

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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 transplantation versus no transplant in patients above 70 with multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e20509 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e20509-e20509

Author(s):

Christopher Lemieux ◽

Lori S. Muffly ◽

David Joseph Iberri ◽

Andrew Rezvani ◽

Robert Lowsky ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Risk ◽

Progression Free Survival ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Free Survival ◽

First Line Therapy ◽

Included Patient

e20509 Background: We evaluated outcomes of patients with multiple myeloma (MM) ≥ 70 years who were seen for Autologous Stem Cell Transplant (ASCT) consult, based on whether they underwent transplant vs. non-transplant treatment. Methods: 138 patients with MM ≥ 70 years (median 71, range 70-78) were evaluated in the BMT clinic from 1/2010 to 11/2019 for a transplant consult. Results: Of the 138 patients, 53 proceeded to ASCT. ASCT was not pursued in 85 patients despite most (79%) being eligible for transplant. Reasons for deferring ASCT in eligible patients included patient preference (48%, n = 32) and physician preference (52%, n = 35). 68 patients were seen during first-line therapy, of which 29 underwent upfront transplant. The remainder were seen at second-line or beyond. There was no difference in baseline characteristics among the 113 patients with available follow-up (ASCT = 53, non-ASCT = 60), including median age (71 vs. 72 years, p = 0.4), high-risk cytogenetics (41% vs. 31%, p = 0.4), high-risk HCT-CI (32% vs. 20% p = 0.2), and ISS stage III (34% vs. 27%, p = 0.6). In the 53 patients who underwent transplant, conditioning melphalan dose was 200 mg/m2 (75%, n = 40) and 140 mg/m2 (25%, n = 13). Day 100 transplant related mortality was 0% (n = 0). Progression-free survival (PFS) and overall survival (OS) were compared in patients who were seen for consultation within 1 year of diagnosis (n = 80). With a median follow-up of 27 months, median PFS amongst patients ≥ 70 years undergoing ASCT (n = 39) was 47 months compared to 34 months in the non-ASCT (n = 41) group, p = 0.006. Median OS was not reached in either group. Estimated 5-years OS was 76% in the ASCT group and 82% in the non-ASCT group (p = 0.6). There was no difference in PFS of patients ≥ 70 undergoing ASCT compared to a cotemporaneous cohort of patients < 70 (n = 639) from our institution (47 vs. 57 months, p = 0.3). Conclusions: Selected patients ≥ 70 years with MM undergoing ASCT have better PFS compared to patients with similar characteristics who do not undergo ASCT. ASCT is safe in this older population and outcomes were similar compared to younger patients. [Table: see text]

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Tandem Autologous Stem Cell Transplants (auto-auto) with or without Maintenance Therapy Versus Single Autologous Transplant Followed by HLA-Matched Sibling Non- Myeloablative Allogeneic Stem Cell Transplant (auto-allo) for Patients (pts) with High Risk (HR) Multiple Myeloma (MM): Results From the Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) 0102 Trial

Blood ◽

10.1182/blood.v116.21.526.526 ◽

2010 ◽

Vol 116 (21) ◽

pp. 526-526 ◽

Cited By ~ 6

Author(s):

Edward A Stadtmauer ◽

Amrita Krishnan ◽

Marcelo C Pasquini ◽

Marian Ewell ◽

Edwin P Alyea ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplant ◽

Chronic Gvhd ◽

Secondary Analysis ◽

Progression Free Survival ◽

Phase Iii ◽

Cell Transplant ◽

Primary Analysis ◽

Hematopoietic Stem

Abstract Abstract 526 The prognosis of patients with high-risk myeloma (HR MM) continues to be dismal, despite the early incorporation of novel agents. Early phase trials of allogeneic hematopoietic stem cell transplant (alloHCT) suggest the possibility of an immunologic graft-versus-myeloma effect that might favorably affect survival. Less toxic reduced-intensity HCT preparative regimens now allow more widespread use of alloHCT in the MM population. BMT CTN 0102 is a phase III multicenter clinical trial that biologically assigned patients to either melphalan 200mg/m2 (MEL 200) auto-auto without (obs) or with 1 year of thalidomide and dexamethosone (ThalDex), or an auto-allo approach using MEL 200 followed by alloHCT using 2 Gy total body irradiation. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine and mycophenolate mofetil. Patients were stratified by biological prognostic factors that were considered to be high risk at the time of the trial design: chromosome 13 deletions by metaphase karyotype and beta-2 microglobulin ≥4 mg/dl. The primary endpoint was 3-year progression free survival (PFS). Between December 2003 and March 2007, 710 patients from 43 US centers were enrolled, and 85 fulfilled the criteria of HR MM. Among them, 48 were assigned to auto-auto (24 Thal-Dex and 24 obs) and 37 to auto-allo. Groups differed in age (median 57 y and 51y, p=0.02) but were otherwise balanced. Compliance with second transplant was 65% for auto-auto and 78% for auto-allo. Compliance with ThalDex was poor, so the two auto-auto arms were pooled for the primary analysis. Three-year PFS was 33% (95% Confidence Interval (CI), 22–50%) and 40% (95% CI, 27–60%, p=0.74) and 3-year OS was 67% (95% CI, 54–82%) and 59% (95% CI, 49–78%, p=0.46) for auto-auto and auto-allo, respectively. Corresponding probabilities for 3-year progression/relapse was 53% and 33% (p=0.09), and 3 year treatment-related mortality was 8% and 20% (p=0.3). Among auto-allo patients, probabilities of grade 3–4 acute and chronic GVHD were 9% and 48%, respectively. Among the 59 (31 auto-auto, 28 auto-allo) patients who received second transplant, 3 year PFS was 35% and 46% (p=0.6). Disease response at day 56 after second transplant was 57% for very good partial response (VGPR) or better and 37% for complete response (CR) and near CR (nCR) in the auto-auto group; and 48% (VGPR or better) and 41% (CR+nCR) in the auto-allo group. In conclusion, this planned secondary analysis of a cohort of HR MM patients demonstrated equivalent 3-year PFS and OS for auto-auto and auto-allo in both intention-to-treat and as-treated analyses. However, trends in late PFS and time to progression/relapse suggest further follow-up is needed before final conclusions regarding the utility of auto-allo in this HR cohort can be made. Finally, this study shows the feasibility of an alloHCT approach for HR MM patients and may serve as a platform for future studies seeking to enhance graft-versus-myeloma effects. Disclosures: Stadtmauer: Celgene: Speakers Bureau. Krishnan:Celgene: Speakers Bureau. Qazilbash:Celgene: Speakers Bureau. Vesole:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Giralt:Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau.

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Efficacy and Safety Of Treatments For Relapsed Or Refractory DLBCL: Results Of a Systematic Literature Review

Blood ◽

10.1182/blood.v122.21.5104.5104 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5104-5104 ◽

Cited By ~ 1

Author(s):

Ann Colosia ◽

Peter C Trask ◽

Robert Olivares ◽

Shahnaz Khan ◽

Adeline Abbe ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Meta Analysis ◽

Progression Free Survival ◽

High Dose Chemotherapy ◽

High Dose ◽

Cell Transplant ◽

Efficacy And Safety ◽

Free Survival ◽

Career Development Award

Abstract Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphoma (NHL) cases in Western countries. Although two-thirds of patients may be cured with combination chemotherapy, in the event of treatment failure and for those who are refractory to treatment, survival is usually measured in months. Several therapeutic modalities have been utilized for patients with relapsed or refractory disease, but among patients who are not eligible for high-dose chemotherapy with stem cell transplant, a comprehensive assessment of efficacy and safety is lacking. This systematic literature review (SLR) was designed to exhaustively collect and review information on the clinical efficacy and safety of the different interventions used in the treatment of refractory or relapsed DLBCL, and if possible to perform a meta-analysis. Methods Electronic databases (PubMed, Cochrane Library, Embase) were searched for relevant studies published from 1997 to August 2, 2012. In addition, conference abstracts, bibliographic reference lists of included articles and recent reviews, and the Clinicaltrials.gov database were searched for phase 2, 3, or 4 studies displaying results, potentially unpublished in peer-reviewed journals. Main efficacy outcomes included objective response rate (ORR), complete response, partial response, duration of response, progression-free survival (PFS), and overall survival (OS). Safety endpoints focused on grade 3/4 toxicities and treatment discontinuation due to toxicity. Studies had to report on relapsed or refractory DLBCL after at least one standard treatment and patients who were not eligible to receive high-dose chemotherapy or stem cell transplant (autologous or allogeneic). Mixed type NHL studies were required to report DLBCL outcomes separately for inclusion. Results A total of 3,308 publications were identified in the first pass of a broad SLR on NHL; of these, 57 provided relevant data for DLBCL representing 54 unique studies. Of the 54 studies, there was 1 phase 3 study, 33 phase 2 studies, and 4 phase 1/2 studies (15 studies did not report the study phase and 1 was an observational study). Six studies were comparative (3 randomized trials; 3 nonrandomized trials) with two treatment arms; 48 studies were single arm. Of the 48 regimens evaluated, few regimens were represented more than once. Overall survival and PFS were often not reported or not reported separately for the patients with DLBCL in studies that enrolled patients with any of the multiple lymphoma histologies. Refractory and relapsed criteria were often not defined, and definitions were heterogeneous when available. The ORR from the few comparative studies ranged from 27% to 100%, with most estimates between 40% and 70%. PFS with low and high doses of obintuzumab was 2 months and 3 months, respectively in one study, and OS was 4 months with MEP and 7 months with C-MEP in another study. There was a common regimen in two of the randomized controlled trials, but the patient populations in these studies differed too greatly to allow a valid meta-analysis to be performed. In the single-arm studies, ORR ranged from 11% to 100%, with the estimates evenly distributed across that range. Progression-free survival was approximately 1 to 10 months. Reported median OS ranged from 1 to 13 months. Main safety concerns included thrombocytopenia, leukopenia, and neutropenia. Conclusions There is a high unmet need for effective therapies for patients with relapsed or refractory DLBCL who are ineligible for stem cell transplant. Although numerous regimens have been evaluated in single-arm trials and a handful in comparative studies, there is no clearly superior regimen for patients with relapsed or refractory DLBCL, especially in third- and later lines of therapy. FA is supported by a Clinical Career Development Award from the Lymphoma Research Foundation Disclosures: Colosia: RTI Health Solutions: Employment. Trask: Sanofi: Employment. Olivares: Sanofi: Employment. Khan: RTI Health Solutions: Employment. Abbe: Sanofi: Employment. Police: RTI Health Solutions: Employment. Njue: RTI Health Solutions: Employment. Wang: RTI Health Solutions: Employment. Sherrill: RTI Health Solutions: Employment. Ruiz-Soto: Sanofi: Employment. Kaye: RTI Health Solutions: Employment. Awan: Lymphoma Research Foundation (Career Development Award): Research Funding.

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Nontransplant Treatment Outcomes with Generic Novel Agents in Newly Diagnosed Multiple Myeloma Patients

Blood ◽

10.1182/blood.v126.23.5382.5382 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5382-5382

Author(s):

Chandran K Nair ◽

Vineetha Raghavan ◽

Atanu Bhattacharjee ◽

Satheesh Babu ◽

Sangeetha Nayanar

Keyword(s):

Treatment Outcomes ◽

Stem Cell Transplant ◽

Progression Free Survival ◽

Novel Agents ◽

Cell Transplant ◽

Free Survival ◽

Entire Cohort ◽

Grade 3 ◽

Stage 1

Abstract Introduction Introduction of novel agents (Immunomodulators-thalidomide/lenalidomide and proteasome inhibitors-bortezomib) has really changed the treatment outcomes in myeloma patients. This is applicable to patients both eligible and ineligible for autologous stem cell transplant. In developing countries, like India, access to the generic forms makes it easy for patients to have treatment with all types of novel agents. In this study, we did a retrospective audit of the treatment outcomes with the generic forms of novel agents in a group of transplant ineligible patients. Methodology All newly diagnosed myeloma cases from January 2011 to December 2014, who did not undergo stem cell transplant, were included for the study. Criteria for diagnosis and treatment response were according to the latest IMWG guidelines. Baseline demographic data and details regarding CRAB criteria, Performance Status (PS), comorbidities, type and duration of treatment, and toxicity were recorded. Toxicity was graded according to CTCAE v 4. Only the maximum grade of a particular toxicity per patient has been reported. Dates of death if applicable was noted, and if patients were alive, date of last follow up was documented. Survival was analysed by non-parametric methods (Kaplan Meier and Cox proportional hazard model) and the variables considered were 'treatment completed' versus 'not completed', 'response' (PR or more) versus 'no response', 'maintenance received' versus 'not received', 'age ≤65 years' versus 'age >65 years', and international staging system (ISS) ' stage 1' versus 'stage 2 or 3'. Analysis was performed with R v 3.2.0 (http://cran.r-project.org.) Results One hundred and nineteen patients (53 males, 66 females) with median age of 62 years (range 44-85) were included as per eligibility criteria. Eighty four (70%) patients had IgG, and 21 (17.6%) had IgA, and 14 (11.7%) had light chain myeloma. Twenty two (18.4%) patients were in ISS stage 1, 36 (30%) were in stage 2 and 39 (32.7%) were in stage 3, with data missing in 22 patients. Fifty seven (47.9%) patients were having comorbidity. Ninety seven patients (81%) were having PS ≤ 2 and 21(17.6%) had PS >2. Lenalidomide based regimen was given in 29 patients, thalidomide based in 65 and bortezomib based in 25 patients. Overall response (PR or more) was documented in 74 (72%), out of 102 evaluable patients. VGPR or more was documented in 56 (55%), and PR in 18(17.6%) patients. Seventy three (61%) patients had some form of toxicity. Grade 3 nonhematologic toxicity occurred in 7 patients (peripheral neuropathy in 2, diarrhea in 2 and DVT in 3), grade 4 in none. Grade 3-4 hematologic toxicity occurred in 8 patients (grade 3 anemia and thrombocytopenia in 3 each, and grade 4 thrombocytopenia in 2 patients). Median follow up duration was 22 months. Estimated 3 year OS for entire group was 60% (95 % CI 47-77%) (Figure 1). Median PFS was 22 months (95 % CI 19- 25) (Figure 2). Variables significantly predicting OS were, treatment completed or not (47 Vs 32 months, HR= 0.372, P= 0.011) and age ≤ 65 versus age >65(47 Vs 31 months, HR= 4.15, P<0.001). Similarly for PFS the significant variables were response or not (24 Vs 7 months, HR= 4.89, P<0.001) and ISS stage 1 Vs stage 2 or 3 (25 Vs 19 months, HR=2.39, P=0.021). Conclusion Treatment with the generic forms of novel agents leads to comparable response rates and survival in patients with myeloma. So, use of these agents with lower cost seems justifiable in the real world practice where it may be difficult to access the innovators for the exuberant cost. Figure 1. Overall survival for the entire cohort Figure 1. Overall survival for the entire cohort Figure 2. Progression free survival for the entire cohort Figure 2. Progression free survival for the entire cohort Disclosures No relevant conflicts of interest to declare.

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Long-Term Outcomes of Allogeneic Stem Cell Transplant in Peripheral T-Cell Lymphoma

Blood ◽

10.1182/blood-2018-99-114288 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4672-4672

Author(s):

Dipenkumar Modi ◽

Seongho Kim ◽

Abhinav Deol ◽

Asif Alavi ◽

Lois Ayash ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

Progression Free Survival ◽

T Cell Lymphoma ◽

Cell Transplant ◽

Peripheral T Cell Lymphoma ◽

Free Survival

Abstract Introduction: Peripheral T-cell Lymphoma represents a heterogeneous group of lymphoid malignancies characterized by poor prognosis with 5-year overall survival (OS) about 25% with conventional chemotherapy. Autologous stem cell transplant (Auto-SCT), as consolidation, is often considered in first complete remission (CR), providing between 30 to 40% long term disease-free survival. However, patients receiving Auto-SCT in second CR or with refractory disease have poor outcomes with progression-free survival ranging from 15-20% to 0%, respectively. In such cases, allogeneic stem cell transplant (Allo-SCT) may provide long term disease control. We intended to study outcomes of Allo-SCT in peripheral T-cell lymphoma patients. Methods: We have retrospectively evaluated long-term outcomes of adult peripheral T-cell lymphoma patients at Karmanos Cancer Institute. The objectives were to determine GVHD rate, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) following Allo-SCT. Results: Between January 2005 and December 2017, 39 patients underwent Allo-SCT. The different diagnoses included peripheral T-cell lymphoma, not-otherwise-specified (n=16), angioimmunoblastic T-cell lymphoma (n=8), anaplastic T-cell lymphoma (n=8), hepatosplenic T-cell lymphoma (n=2), cutaneous T-cell (n=3) and NK cell lymphoma (n=2). The median age at transplant was 50 years (range, 21-67). The median number of prior therapies was 2 (range, 1-5) and 12 patients (31%) had failed prior Auto-SCT. Sixteen patients (41%) were in CR and 2 (5%) were in partial remission at the time of Allo-SCT, whereas 12 (31%) patients had relapsed disease and 9 (23%) had refractory disease. Twenty-one patients (54%) received matched related and 18 patients (46%) had unrelated Allo-SCT. Myeloablative conditioning regimen was used in 22 patients (56%), whereas reduced intensity regimen was used in 17 (44%) patients. Grade III-IV acute GVHD occurred in 25.6% (95% CI, 13.2-40.1%) and chronic GVHD occurred in 41% (95% CI, 25.1-56.3%). After a median follow-up of 3.08 years (95% CI, 2.49-7.28) among surviving patients, the estimated probabilities of 3-year OS and PFS were 35.9% (95% CI, 22.4-57.6%) and 32.5% (95% CI, 19.9-53%), respectively. The 3-year relapse rate was 23.9% (95% CI, 11.5-38.7%), whereas NRM was 35.9% (95% CI, 21.1-50.9%). No difference in OS and PFS was noticed in patients receiving Allo-SCT in first CR compared with patients receiving Allo-SCT beyond first CR (p=0.81; p=0.94). Similarly, no difference in OS and PFS was noted in patients with Allo-SCT followed by failed prior Auto-SCT compared with patients with upfront Allo-SCT (p=0.31; p=0.47). Seventeen of 39 patients were alive and 22 were deceased (n=7 disease relapse; n=15 NRM). Out of 39 patients, 13 (33%) alive patients are free of relapse and GVHD as of data analysis. Conclusion: Our study suggests that Allo-SCT is a viable treatment option for peripheral T-cell lymphoma and appears to provide cure in these highly selected patients. The survival advantage was noted in patients beyond first remission; therefore, it should be considered in all transplant eligible patients. In addition, certain proportion of patients who failed prior Auto-SCT benefited from Allo-SCT, which points towards potential role of graft-versus-lymphoma effect. Disclosures Deol: Novartis: Consultancy; Kite Pharmaceuticals: Consultancy.

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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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Radioimmunotherapy with 131-I tositumomab enhanced survival in good prognosis relapsed and high-risk diffuse large B-cell lymphoma (DLBCL) patients receiving high-dose chemotherapy and autologous stem cell transplantation

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8013 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8013-8013 ◽

Cited By ~ 6

Author(s):

J. Vose ◽

P. Bierman ◽

G. Bociek ◽

F. Loberiza ◽

C. Enke ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplant ◽

B Cell Lymphoma ◽

Autologous Stem Cell Transplant ◽

Good Prognosis ◽

Phase Iii ◽

Cell Transplant ◽

Outpatient Basis

8013 Background: The 5-year overall survival (OS) for pts with relapsed chemosensitive DLBCL with standard transplantation is approximately 40–50%. We previously piloted the addition of standard outpatient radioimmunotherapy (RIT) with 131-I tositumomab to the transplant regimen for patients with relapsed chemoresistant NHL. This phase I study demonstrated a 3 yr OS of 55% in these poor prognosis patients (JCO 23: 461–467, 2005). The current study is a follow-up phase II study in good prognosis relapsed and high risk DLBCL patients using 131-I tositumomab with BEAM (BCNU, etoposide, cytarabine, and melphalan) followed by an autologous stem cell transplant. Methods: Forty patients were accrued to the study between 2000–2005. The patients had a median age of 54 yrs (26–75) and all had a diagnosis of DLBCL. The patients had a median of two prior chemotherapies before transplant and 88% had received prior Rituximab. All patients had chemotherapy sensitive disease at the time of stem cell transplant. Following stem cell collection, all patients received a stem cell preparative regimen of 75 cGy total body dose of 131-I tositumomab (dosimetric dose day -19 and therapeutic day -12) followed by a standard BEAM transplant regimen. Autologous unpurged stem cells were infused on day 0. The median time of follow-up of the survivors is 28 months (3–68). Results: Seventy eight percent of the patients had a complete remission following the transplant. The 3 year progression free survival (PFS) is 70% (95% CI - 48 - 84%) and the 3 year OS is 81% (95% CI - 61 - 91%). The entire transplant can be delivered on an outpatient basis. No increased toxicity compared to a similar cohort receiving BEAM alone could be detected. Conclusions: The addition of 131-I tositumomab to BEAM and autologous stem cell transplant for relapsed or high-risk chemosensitive DLBCL produces a 3-yr OS of 81% without excess toxicity. This compares favorably to historical controls. This regimen is currently being tested in a phase III trial in the BMT/CTN of Rituximab/BEAM vs. 131-I tositumomab/BEAM in patients with relapsed chemosensitive DLBCL. No significant financial relationships to disclose.

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Analysis of Outcome after Autologous Stem Transplantation in Patients with Newly Diagnosed Myeloma: Comparison of Different Induction Regimens.

Blood ◽

10.1182/blood.v108.11.3079.3079 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3079-3079 ◽

Cited By ~ 4

Author(s):

Shaji Kumar ◽

Martha Q. Lacy ◽

Angela Dispenzieri ◽

Suzanne R. Hayman ◽

S. Vincent Rajkumar ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Induction Therapy ◽

Stem Cell Transplant ◽

Single Agent ◽

Progression Free Survival ◽

Initial Therapy ◽

Cell Transplant ◽

Newly Diagnosed ◽

Free Survival

Abstract Background: Autologous stem cell transplantation (SCT) improves survival in patients (pts) with multiple myeloma (MM). We have previously demonstrated that the degree of response at transplant does not impact on the outcome of transplant. However, newer induction regimens such as thalidomide and dexamethasone (Thal-Dex) result in higher response rates compared to previously used regimens such as single agent dexamethasone or vincristine, doxorubicin, and dexamethasone (VAD). We examined the outcome of SCT following three different induction therapies for newly diagnosed MM, namely VAD, single agent Dex, and Thal-Dex. Patients and Methods: 340 patients with MM who received their SCT within 12 mos of diagnosis (median 5.8, range 3–12) were studied. Patients receiving more than one induction therapy as well as those in whom thalidomide was added to dexamethasone for lack of response were excluded from the analysis. There were 105 pts in the VAD group, 140 in the Dex group and 95 in the Thal-Dex group. Responses were defined using standard criteria. Results: The study cohort consisted of 209 males (59%), with a median age of 57 years (range 30–76) at transplant. Baseline characteristics were similar in the 3 groups, except for lower age in the VAD group (median 55.8) compared to Dex (59.6) and Thal Dex (57.4) and shorter time to transplant in the Dex group (5.4 m) compared to VAD (6.4) and Thal Dex (5.9). Markers of disease activity pre-transplant, including B2M and marrow plasma cell percentage were higher in the Dex group compared to either VAD or Thal Dex. The proportion of patients with any response to induction therapy was lower in the Dex group compared to the other two. All pts in the Dex and the Thal-Dex groups received melphalan only conditioning compared to 70% in the VAD group, the rest receiving Melphalan/TBI. An objective response was achieved after SCT in 96%, 97%, and 98% of pts in the VAD, Dex and Thal-Dex groups respectively (P=0.8). A complete response to SCT was seen in 49% of patients in VAD group, 45% among those in the Dex group and 38% among those in the Thal Dex group (P=0.38). There was no difference in the median progression free survival after transplant (P=0.21) or overall survival from diagnosis (P=.34) between the three groups. The proportion free from progression at 2 years post transplant was 54%, 55% and 46% for Dex, VAD and Thal-Dex respectively. The proportion surviving at 4 years from diagnosis was 64%, 65.4% and 72% respectively for the three groups. Conclusion: We did not observe any difference in the response rates including complete responses to SCT in the three groups with nearly all pts in each group achieving a response. The progression free survival and overall survival appear to be comparable between the three groups. The results from initial therapy cannot be compared between the three regimens since the study population is restricted to patients reaching stem cell transplant. Within the limits of the study, there does not appear to be any long term impact of the initial therapy for the patients going onto an early stem cell transplant. Figure Figure

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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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