0
selected
-
1.
Outcomes of Patients With Classic Hodgkin Lymphoma Who Relapsed After Autologous Stem Cell Transplant
Tun, A. M., Wang, Y., Matin, A., Inwards, D. J., Habermann, T. M., Micallef, I., Johnston, P. B., Porrata, L., Paludo, J., Bisneto, J. V., et al
HemaSphere. 2023;7(4):e869
Abstract
Immune checkpoint inhibitors (ICIs) and brentuximab vedotin (BV) are novel agents for classic Hodgkin lymphoma, including relapse after autologous stem cell transplant (ASCT). However, their impact on survival post-ASCT relapse, in comparison with conventional therapy, is less known due to the lack of randomized controlled trials. Clinical characteristics and outcomes of 115 patients with relapse (or progression) after ASCT are studied. After a median follow-up of 8.59 years from post-ASCT relapse, the median progression-free survival (PFS) and overall survival (OS) were 0.91 and 5.07 years, respectively. Median lines of therapy after post-ASCT relapse was 2 (range, 1-12). The median PFS was not reached (NR) versus 1.11 versus 0.50 versus 0.85 versus 0.78 years (P = 0.006) and OS was NR versus 7.60 versus 3.08 versus 3.51 versus 3.17 years (P = 0.28) in patients first treated with ICIs versus BV versus investigational agents versus chemotherapy versus radiation therapy (RT). First-line treatment with novel agents (ie, ICIs and BV) was associated with superior outcomes compared with investigational agents and chemotherapy/RT with a median PFS of 1.65 versus 0.50 versus 0.79 years (P = 0.003) and a median OS of 7.60 versus 3.08 versus 3.32 years (P = 0.08). Regardless of lines of therapy, the treatment with ICIs had the most favorable outcome with a median PFS and OS of 3.98 and NR years, respectively. Allogeneic stem cell transplant (allo-SCT) was done in 23 patients (20%), and the median post-allo-SCT PFS and OS were 1.31 and 2.35 years, respectively. In conclusion, survival following post-ASCT relapse improves significantly when patients receive novel agents.
-
2.
Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant
Scordo, M., Wang, T. P., Ahn, K. W., Chen, Y., Ahmed, S., Awan, F. T., Beitinjaneh, A., Chen, A., Chow, V. A., Dholaria, B., et al
JAMA oncology. 2021
-
-
-
Free full text
-
-
Editor's Choice
Abstract
IMPORTANCE Primary central nervous system lymphoma (PCNSL) requires induction and consolidation to achieve potential cure. High-dose therapy and autologous hematopoietic cell transplant (AHCT) is an accepted and effective consolidation strategy for PCNSL, but no consensus exists on the optimal conditioning regimens. OBJECTIVE To assess the outcomes in patients with PCNSL undergoing AHCT with the 3 most commonly used conditioning regimens: thiotepa/busulfan/cyclophosphamide (TBC), thiotepa/carmustine (TT-BCNU), and carmustine/etoposide/cytarabine/melphalan (BEAM). DESIGN, SETTING, AND PARTICIPANTS This observational cohort study used registry data from the Center for International Blood and Marrow Transplant Research registry. The Center is a working group of more than 380 transplantation centers worldwide that contributed detailed data on HCT to a statistical center at the Medical College of Wisconsin, Milwaukee. The participant data were from 603 adult patients with PCNSL who underwent AHCT as initial, or subsequent, consolidation between January 2010 and December 2018. Patients were excluded if they had a non-Hodgkin lymphoma subtype other than diffuse large B-cell lymphoma, systemic non-Hodgkin lymphoma, or HIV; received an uncommon conditioning regimen; or were not in partial remission or complete remission prior to AHCT. Statistical analysis was performed from July 5, 2020, to March 1, 2021. INTERVENTIONS Patients received 1 of 3 conditioning regimens: TBC (n?=?263), TT-BCNU (n?=?275), and BEAM (n?=?65). MAIN OUTCOMES AND MEASURES The primary outcome was progression-free survival. Secondary outcomes included hematopoietic recovery, incidence of relapse, nonrelapse mortality, and overall survival. RESULTS Of 603 patients, the mean age was 57 (range, 19-77) years and 318 (53%) were male. The 3-year adjusted progression-free survival rates were higher in the TBC cohort (75%) and TT-BCNU cohort (76%) compared with the BEAM cohort (58%) (P?=?.03) owing to a higher relapse risk in the BEAM cohort (hazard ratio [HR], 4.34; 95% CI, 2.45-7.70; P?.001). In a multivariable regression analysis, compared with the TBC cohort, patients who received TT-BCNU had a higher relapse risk (HR, 1.79; 95% CI, 1.07-2.98; P?=?.03), lower risk of nonrelapse mortality (NRM) (HR, 0.50; 95% CI, 0.29-0.87; P?=?.01), and similar risk of all-cause mortality more than 6 months after HCT (HR, 1.54; 95% CI, 0.93-2.55; P?=?.10). Age of 60 years or older, Karnofsky performance status less than 90, and an HCT-comorbidity index greater than or equal to 3 were associated with lower rates of survival across all 3 cohorts. Subgroup analyses demonstrated that patients aged 60 years and older had considerably higher NRM with TBC. CONCLUSIONS AND RELEVANCE In this cohort study, thiotepa-based conditioning regimen was associated with higher rates of survival compared with BEAM, despite higher rates of early toxic effects and NRM; these findings may assist clinicians in choosing between TBC or TT-BCNU based on patient and disease characteristics.
PICO Summary
Population
Adults with primary central nervous system lymphoma (PCNSL) who underwent autologous transplantation as initial, or subsequent, consolidation and were reported to the CIBMTR registry (n=603)
Intervention
Thiotepa/busulfan/cyclophosphamide conditioning (TBC, n=263), thiotepa/carmustine conditioning (TT-BCNU, n=275)
Comparison
Carmustine/etoposide/cytarabine/melphalan conditioning (BEAM, n=65).
Outcome
The mean age was 57 (range, 19-77) years and 318 (53%) were male. The 3-year adjusted progression-free survival rates were higher in the TBC cohort (75%) and TT-BCNU cohort (76%) compared with the BEAM cohort (58%), owing to a higher relapse risk in the BEAM cohort (hazard ratio [HR], 4.34). In a multivariable regression analysis, compared with the TBC cohort, patients who received TT-BCNU had a higher relapse risk (HR, 1.79), lower risk of nonrelapse mortality (NRM) (HR, 0.50), and similar risk of all-cause mortality more than 6 months after HCT (HR, 1.54). Age of 60 years or older, Karnofsky performance status less than 90, and an HCT-comorbidity index greater than or equal to 3 were associated with lower rates of survival across all 3 cohorts. Subgroup analyses demonstrated that patients aged 60 years and older had considerably higher NRM with TBC.
-
3.
Outcomes of Autologous Stem Cell Transplant Consolidation in Primary CNS Lymphoma: A Mayo Clinic Experience
Khurana, A., Micallef, I. N., LaPlant, B. R., Patrick O'Neill, B., Habermann, T. M., Ansell, S. M., Inwards, D. J., Porrata, L. F., Paludo, J., Bisneto, J. C. V., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
A paucity of randomized phase 3 clinical trials in primary central nervous system lymphoma (PCNSL) has resulted in no uniform consensus on the optimal strategy for consolidation and conditioning regimens for autologous stem cell transplant (ASCT). The last two decades have witnessed a preference for thiotepa-based conditioning regimens due to superior CNS penetration. We retrospectively evaluated outcomes of PCNSL patients who underwent ASCT at Mayo Clinic, Rochester over the last two decades, and the impact of thiotepa (TT) based conditioning regimens. Fifty-six patients underwent transplant for PCNS lymphoma, with 25 and 31 patients receiving BEAM (non-thiotepa) and BCNU/TT based conditioning, respectively. All patients received high-dose methotrexate based induction therapy. While the BCNU/TT group had higher risk disease features such as high International Extranodal Lymphoma Study Group (IELSG) prognostic score, elevated CSF protein and older patient population, there was no significant difference at 2 years post-transplant in PFS (BEAM 68.0% [46.1-82.5] vs. BCNU/TT, 65.5% [45.2-79.8], (p?=?0.99)), or OS (84.0% [62.8-93.7] in the BEAM group vs. 81.6% [61.3-91.9] in the BCNU/TT group, (p?=?0.95)). Disease response status before transplant significantly impacted the outcomes as those in complete remission(CR) had an OS at 2 years post-transplant of 94.7% (68.1-99.2) in BEAM group and 90.5% (67.0-97.5) in BCNU/TT group as compared to those in partial response (PR), 57.1% (17.2-83.7) in BCNU/TT group, and 50.0% (11.1-80.4) in the BEAM group, respectively (p <0.0001). Our retrospective cohort adds to the currently available literature and identifies the disease status before transplant as a significant factor impacting survival.
-
4.
A phase 1 trial of <sup>90</sup>Y-Zevalin radioimmunotherapy with autologous stem cell transplant for multiple myeloma
Dispenzieri, A., D'Souza, A., Gertz, M. A., Laumann, K., Wiseman, G., Lacy, M. Q., LaPlant, B., Buadi, F., Hayman, S. R., Kumar, S. K., et al
Bone Marrow Transplantation. 2017;52(10):1372-1377
Abstract
This phase 1 study (clinical trial NCT00477815) was conducted to determine the maximum tolerated dose (MTD) of yttrium-90 ibritumomab tiuxetan (90Y-Zevalin) with high dose melphalan (HDM) therapy in multiple myeloma (MM) patients undergoing autologous stem cell transplantation (ASCT). In a 3+3 trial design, 30 patients received rituximab 250mg/m2 with indium-111 ibritumomab tiuxetan (111In-Zevalin) for dosimetry (day -22); rituximab 250mg/m2 with escalating doses of 90Y-Zevalin (day -14); melphalan 100mg/m2 (days -2,-1) followed by ASCT (day 0) and sargramostim (GM-CSF, day 0) until neutrophil engraftment. Each patient's 111In-Zevalin dosimetry data were used to calculate the dose of 90Y-Zevalin (in mCi) to deliver 10, 12, 14, 16, 18 or 20Gy to the liver. Dose limiting toxicities were seen in 3 patients. The overall response rate was 73% (22/30) with stringent complete response in 2 patients; complete response, 5; very good partial response, 12; and partial response, 3. The median PFS was 16.5 months and the median overall survival was 63.4 months. In MM, the MTD of 90Y-Zevalin with HDM is 18Gy to the liver. The addition of radiation with novel delivery methods such as radioimmunotherapy combined with standard transplant regimens warrants further study.