Autologous Hematopoietic Cell Transplantation In Multiple Myeloma Patients Age 70 Years and Older.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4576-4576
Author(s):  
Qaiser Bashir ◽  
Wei Wei ◽  
Alexandre Chiattone ◽  
Gabriela Rondon ◽  
Simrit Parmar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Disease Response ◽  
Autologous Hematopoietic Cell Transplantation ◽  
Grade Iii

Abstract Abstract 4576 Introduction: High dose chemotherapy followed by autologous hematopoietic cell transplantation (auto HCT) for multiple myeloma (MM) has shown improved survival compared to conventional chemotherapy. However, the larger clinical trials evaluating the role of auto HCT in MM have included patients who are generally younger than 65 years. Here we report the results of MM patients, age ≥70 years, who received auto HCT at our institution. Methods: We retrospectively analyzed 84 patients, who underwent auto HCT between January 1999 and June 2010 at MDACC. Conditioning regimen was Melphalan 140 mg/m2 (MEL 140) (N=9), 180 mg/m2 (MEL 180) (N=20), and 200 mg/m2 (MEL 200) (N=55). Disease response was assessed at day 100 post transplant. Results: Pertinent patient and disease characteristics are summarized in the Table. Median age at transplant was 72 (70-80) years. Median number of prior treatments was 1 (range: 1–8). Median time from diagnosis to transplant was 8.5 (2.4-151) months. No patient was in CR prior to auto HCT. Median CD34+ cell count and TNC was 4.56 (0.72-11.1) × 106/kg and 10.53 (2.25-57) ×108/kg, respectively. Median follow up is 2 (0.1-7.3) years. Grade III-IV organ toxicity was seen in 35 (51%) patients. Grade III-IV toxicity in patients who received MEL 140, MEL 180, and MEL 200 was 25%, 45%, and 44%, respectively (p value > 0.05). Non-relapse mortality (NRM) at 100 days was 2%. Two patients died in first 100 days. Disease response in evaluable patients (N=79) at day 100 was: CR=15 (19%); VGPR=7 (9%); PR=41 (52%); and SD=10 (13%). Median progression free survival (PFS) and overall survival (OS) from auto HCT was 2.1 years (95% CI 1.78–3.69) and 5.6 years (95% CI 5.51-NA), respectively. 2-year PFS and OS were 56% (95% CI 0.44–0.71) and 80% (95% CI 0.7–0.91), respectively. There was no difference in NRM, PFS, or OS in different MEL groups. Similarly there was no difference in TRM, PFS, and OS in patients ≥ 75 years compared to the patients < 75 years. Conclusion: Auto HCT in myeloma patients age ≥ 70 years is safe and feasible. Toxicity, NRM, response and survival were comparable to younger myeloma patients. The age alone should not be a contraindication for auto HCT. Disclosures: Shah: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Novartis: Research Funding. Orlowski:Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Consultancy, Research Funding. Weber:Novartis-unpaid consultant: Consultancy; Merck- unpaid consultant: Consultancy; Celgene- none for at least 2 years: Honoraria; Millenium-none for 2 years: Honoraria; Celgene, Millenium, Merck: Research Funding. Giralt:Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau.

Improved outcomes with maintenance therapy after salvage autologous hematopoietic cell transplantation (AHCT) in multiple myeloma: A CIBMTR study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8022-8022
Author(s):  
Oren Pasvolsky ◽  
Raphael Fraser ◽  
Noel Estrada-Merly ◽  
Moshe Yeshurun ◽  
Uri Rozovski ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Improved Outcomes ◽  
Autologous Hematopoietic Cell Transplantation ◽  
Maintenance Group

8022 Background: Maintenance therapy in multiple myeloma (MM) after first autologous hematopoietic cell transplantation (AHCT1) is considered standard of care. Data regarding maintenance therapy after a salvage AHCT (AHCT2) in the setting of relapsed MM are scarce. Therefore, we used data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to examine the use of maintenance therapy after AHCT2 in MM patients and its effect on post-transplant patient outcomes. Methods: We included US adult MM patients who underwent AHCT2 after melphalan conditioning regimen from 2010-2018, and excluded patients who underwent tandem transplants. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Cox proportional hazards models were developed to study the main effect (maintenance use) with other covariates of interest including age, sex, race, performance status, HCT-comorbidity index, MM subtype, stage, creatinine, cytogenetic, conditioning melphalan dose, disease status at transplant, and time from AHCT1 to AHCT2. Results: Of 522 patients, 342 received maintenance therapy and 180 did not after AHCT2. Baseline characteristics were similar between the two groups. Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Common maintenance regimens included immunomodulatory drugs (IMID)-lenalidomide (N = 145, 42%) or pomalidomide (N = 46, 13%) and proteasome inhibitor, bortezomib (N = 45, 13%). Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7-3.9)% vs 9.9 (5.9-14.9)%, p < 0.001, REL 70.2 (64.4-75.8)% vs 80.3 (73.6-86.3)%, p 0.003, PFS 27.8% (22.4-33.5) vs. 9.8% (5.5-15.2), p < 0.001, and OS 54% (47.5-60.5) vs 30.9% (23.2-39.2) p < 0.001, respectively. IMID-containing maintenance regimens were associated with an improved 5-year PFS and OS compared to other maintenance regimens. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis, including NRM: hazard ratio (HR) 0.19 (0.08-0.44), p 0.0001, REL: HR 0.58 (0.47-0.72), p < 0.0001, PFS HR 0.52 (0.43-0.64), p < 0.0001, and OS HR 0.46 (0.36-0.60), p < 0.0001. We conducted additional analyses to investigate a possible selection bias in the maintenance group including landmark analysis at 100-days and 6-months post-AHCT2 as well as a subgroup analysis of patients who received melphalan 200mg/m2 as conditioning for AHCT2 (as a surrogate for fitness)- all these analyses also showed improved outcomes in the maintenance group. Second cancers were reported in 17 (5%) patients in the maintenance group and 6 (3%) patients and no-maintenance group (p 0.39). Conclusions: Maintenance therapy after AHCT2 is associated with superior outcomes in MM patients.

scholarly journals Panobinostat As a Maintenance Therapy after Autologous Hematopoietic Cell Transplantation for Patients with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3189-3189
Author(s):  
Taiga Nishihori ◽  
Rachid Baz ◽  
Leonel Ochoa ◽  
Omar Alexis Castaneda Puglianini ◽  
Kenneth H. Shain ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Advisory Committees ◽  
Autologous Hct ◽  
Autologous Hematopoietic Cell Transplantation

Background: Autologous hematopoietic cell transplantation (HCT) followed by maintenance therapy with an immunomodulatory agent or a proteasome inhibitor remains an important strategy for upfront treatment in multiple myeloma (MM) with progression-free survival (PFS) and overall survival (OS) advantage. We designed a two-arm, open-label prospective study to examine the safety and tolerability of two different dosing schedules of an oral pan-histone deacetylase inhibitor, panobinostat (pano) as an alternative maintenance therapy option in patients with MM (NCT02722941). Methods: A total of 30 MM patients who underwent autologous HCT within the preceding 90 to 180 days were enrolled at Moffitt Cancer Center using a sequential alternating allocation to starting dose of either Cohort A: 20 mg PO 3/week, q 2 weeks on a 28-day cycle, or Cohort B: 10 mg PO daily for 7 days, q 2 weeks on a 28-day cycle, for 12 cycles. Dose level -1 was cohort A: 15 mg 3/week; and cohort B: 10 mg 4/week. Patients with clinically significant cardiac diseases, bradycardia, QTc > 470 msec, bifascicular block were ineligible. EKG was performed on pre- and post-dose on day 1 & 5 of cycle 1, and pre-dose on day 1 of cycles 2-4. Relative dose intensity (RDI), a ratio of amount of drug actually delivered in mg over the amount of planned dose in mg, was calculated to evaluate the treatment feasibility as a surrogate measure. Results: The median age of the entire cohort was 60 (range, 40-73) years with a male/female = 18/12. Disease characteristics are summarized in the Table. Patients initiated pano maintenance at a median of 131 (range 91 - 178) days after autologous HCT. As of 8/1/2019, 16 patients (8 in each cohort) completed full 12 cycles of pano. The RDI for the entire cohort, cohort A, and cohort B was 94.1% (33,750mg/35,860, 98% (16,350mg/16,680mg), and 90.7% (17,400mg/19,180mg), respectively. One patient in cohort A had dose reduction, and 6 patients in cohort B had dose reductions with cytopenias (43%) and GI toxicities (43%) being the most common reasons. No patients required dose modifications due to QT prolongation thus far. There were 3 possibly treatment-associated serious adverse events (pneumonia=2; colitis=1) but all patients successfully resumed pano. Three patients progressed while on pano maintenance. No mortality has been observed thus far. Ten patients are still on pano treatment. The median follow-up is 11 (range, 1-29) months. Conclusions: RDI is 90% overall and panobinostat as a single oral maintenance agent either at 20 mg three times per week or 10 mg po daily for 7 days on alternating weeks appears to be overall well tolerated. There were more dose reductions required in the 10 mg starting dose (cohort B). Panobinostat is a safe alternative for maintenance therapy after autologous HCT. Longer follow-up is needed to confirm the utility of this approach and updated results will be presented at the meeting. Disclosures Nishihori: Novartis: Research Funding; Karyopharm: Research Funding. Baz:Sanofi: Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Research Funding; Merck: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Shain:Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy. Brayer:Janssen: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Locke:Kite: Other: Scientific Advisor; Novartis: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy. Alsina:Bristol-Myers Squibb: Research Funding; Janssen: Speakers Bureau; Amgen: Speakers Bureau. OffLabel Disclosure: Panobinostat single agent maintenance therapy after autologous hematopoietic cell transplantation for multiple myeloma

Outpatient High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation for Multiple Myeloma Is Associated with a Low Infection Safety Profile.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5070-5070
Author(s):  
Mounzer E. Agha ◽  
Andrew M. Yeager ◽  
Carol Evans ◽  
Nikol Borkowski ◽  
Anne Marie Scekeres ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
High Dose Chemotherapy ◽  
Hematopoietic Cell ◽  
Coagulase Negative Staphylococcus ◽  
High Dose ◽  
Cytomegalovirus Pneumonia ◽  
High Dose Melphalan ◽  
Autologous Hematopoietic Cell Transplantation

Abstract High-dose melphalan (MEL) and autologous hematopoietic cell transplantation (HCT) is now a standard therapy in patients (pts) with multiple myeloma (MM). This HCT procedure is sufficiently tolerable to be performed on either an outpatient (OP) or inpatient (IP) basis. We compared the infection profiles in 16 consecutive pts who underwent OP HCT and 31 consecutive pts who underwent IP HCT for MM over a 24-month period. The median age of each group was comparable (OP 58 yr, range 33–72 yr; IP 59 yr, range 32–74 yr). All pts received MEL 200 mg/m2 before HCT and anti-infective prophylaxis with oral acyclovir, fluconazole and levofloxacin. Empiric treatment of first neutropenic fever in the OP group was imipenem and vancomycin (VAN) and in the IP group was cefepime with addition of VAN for persistent fever and/or positive cultures with VAN-sensitive bacteria. Median time to neutrophils &gt;0.5 x 109/L after HCT was 10 days in both groups (range 8–12 days for OP and 9–12 days for IP). Fever during neutropenia occurred in 7/16 (43.8%) of OP and 16/31 (51.6%) of IP HCT pts. Positive blood cultures (BCs) were identified in 3/7 (42.9%) of the febrile OP and 5/16 (31.3%) of the febrile IP HCT pts. Positive BCs in febrile OP HCT pts were coagulase-negative Staphylococcus (CNS) (2 pts) and Pseudomonas (1 pt). Positive BCs in febrile IP HSCT pts were CNS (2 pts), Streptococcus viridans (1 pt), Enterococcus (1 pt) and Bacillus (1 pt). One febrile OP HCT pt had cytomegalovirus pneumonia, and one afebrile IP HCT pt had a positive BC for CNS. Four febrile IP HCT pts with negative BCs had other infections, including cellulitis (2), facial abscess (1), and Clostridium difficile-associated colitis (CDAC) (1). Two other IP HCT pts (1 with fever and positive BC for CNS, 1 without fever) also had CDAC, for an overall incidence of CDAC of 3/31 (9.7%) after IP HCT. In contrast, no OP HCT pts had CDAC. Overall, the incidence of infections was 4/16 (25%) after OP HCT and 11/31 (35.5%) after IP HCT. We conclude that the infection profile of OP HCT compares favorably with that of IP HCT in pts with MM and is associated with a lower incidence of CDAC.

Busulfan / Melphalan / Bortezomib (Bu-Mel-Vel) Vs. High Dose Melphalan As Conditioning Regimen For Autologous Hematopoietic Cell Transplantation In Multiple Myeloma (MM)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3357-3357 ◽  
Author(s):  
Tulio E. Rodriguez ◽  
Parameswaran Hari ◽  
Patrick J Stiff ◽  
Xiaobo Zhong ◽  
Danielle Sterrenberg ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Maintenance Therapy ◽  
Cell Transplantation ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
High Dose ◽  
High Dose Melphalan ◽  
Autologous Hematopoietic Cell Transplantation

Abstract Background High dose melphalan (MEL) preceding autologous hematopoietic cell transplantation (HCT) for MM continues to be the standard of care. No regimen has been clearly proven superior to MEL 200 mg/m2 (MEL 200). The combination of Busulfan (Bu) and MEL was shown to improve progression free survival (PFS) (Lahuerta, et al; Haematologica. 2010 Nov; 95 (11):1913-20). The combination of bortezomib (Vel) with MEL also demonstrated superior PFS vs. MEL alone using historical controls (Roussel et al; Blood. 2010; 115:32-7). We studied a conditioning regimen combining Bu, MEL and Vel (BuMelVel) in an open label phase II study aimed at improving PFS after HCT for MM. To assess the potential value of this novel regimen, we performed a comparative analysis between BuMelVel and a cohort of patients conditioned with MEL 200 from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Methods Between July 2009 and May 2012, 43 eligible patients received BuMelVel conditioning followed by HCT. Bu was administered daily intravenous (IV) for a total of 4 days with the first 2 days (day -6, -5) at fixed dose of 130 mg/m2 over 3 hours and the subsequent 2 doses (day -4, -3) adjusted to achieve a target area under the concentration-time curve (AUC) total of 20,000 mM* min by performing pharmacokinetic (PK) analysis after the first dose of IV Bu. Mel 140 mg/m2 and Vel 1.6 mg/m2 were administered IV on Day-2 and Day -1 respectively. Outcomes were compared with a contemporaneous North American cohort (n=162) receiving single agent MEL 200 conditioning from the CIBMTR database. Controls were matched on age, sex, Karnofsky performance status (KPS), stage and interval from diagnosis to HCT. Multivariate analysis of Relapse, PFS, and overall survival (OS) was performed. Median follow up of survivors was 25 months. Planned maintenance therapy was not used. Results Age, gender, KPS, isotype, and stage were similar between groups (Table 1.). The MEL 200 cohort had more standard risk patients per Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) (78% vs. 40% in BuMelVel, p <0.0001) and more patients with only 1 prior line of therapy pre-HCT (67% vs. 47%, p = 0.02). Platelet and neutrophil engraftment kinetics were similar. Veno-occlusive disease (VOD) was not observed in the BuMelVel group and there was no non-relapse mortality (NRM). The incidence of relapse and PFS at 1 year were superior in the BuMelVel cohort (Table 1.). OS was similar between the cohorts. In multivariate analysis, PFS was superior in the BuMelVel cohort (HR for relapse/death in MEL 200 =1.87, p=0.04). Lack of a very good partial response or higher (≥VGPR) prior to HCT was associated with inferior PFS whereas lower KPS (<80) and higher international stage were associated with mortality. Conclusion PK directed dosing of Bu can be safely combined with Mel 140 followed by bortezomib without higher risk of VOD or NRM and in the absence of maintenance therapy. Within the constraints of a short follow up and uncontrolled post-transplant salvage therapies on both groups, no difference in OS has yet been observed. This novel conditioning regimen is safe and was associated with superior PFS compared with similarly matched controls and warrants further testing. Disclosures: Rodriguez: Otsuka: Research Funding; Millennium: Research Funding, Speakers Bureau; Celgene: Honoraria, Speakers Bureau. Vesole:Millennium: Speakers Bureau.

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