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R-MPV followed by high-dose chemotherapy with thiotepa-based and autologous stem cell transplantation for newly diagnosed primary central nervous system lymphoma: a single-center experience.

ABSTRACT:

Background

High-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) as a consolidation treatment is a promising approach for eligible patients with newly diagnosed primary central nervous system lymphoma (PCNSL).

Methods

In this retrospective analysis, 22 patients with newly diagnosed PCNSL received chemotherapy with rituximab, methotrexate, procarbazine, and vincristine. Those who showed complete or partial response subsequently received consolidation HDC-ASCT with a thiotepa- based conditioning regimen but did not undergo radiotherapy.

Results

The PCNSL patients had a median age of 57 years (range, 49‒67 yr); of the total patients, 9.1% had a performance status of 2 or higher, and 72.1% had multiple lesions. Approximately 82% of patients received six cycles of induction chemotherapy, which was well tolerated with excellent disease control. The rate of confirmed or unconfirmed complete response increased from 45.5% at the period of interim analysis to 81.8% prior to the initiation of HDC-ASCT. With a median follow-up of 19.6 months (range, 7.5‒56.5 mo), the 2-year progression-free survival and overall survival estimates were 84% and 88%, respectively. No treatment-related deaths occurred. Grade 3 toxicity was recorded in 90.9% of the patients after undergoing the HDC-ASCT, and the most common grade 3 adverse event was febrile neutropenia without sepsis.

Conclusion

The discussed treatment approach is feasible in patients with newly diagnosed PCNSL, yielding encouraging results.

SUBMITTER: Lee JY

PROVIDER: S-EPMC8721461 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportancePrimary 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.ObjectiveTo 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 participantsThis 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.InterventionsPatients received 1 of 3 conditioning regimens: TBC (n = 263), TT-BCNU (n = 275), and BEAM (n = 65).Main outcomes and measuresThe primary outcome was progression-free survival. Secondary outcomes included hematopoietic recovery, incidence of relapse, nonrelapse mortality, and overall survival.ResultsOf 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 relevanceIn 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.

Project description:ObjectiveThe reviewed literature supports a treatment regimen for primary central nervous system lymphoma (PCNSL) that includes induction chemotherapy, followed by one consolidation therapy. High-dose chemotherapy supported by autologous stem-cell transplantation (ASCT) is the most studied option, but its effects are controversial. The aim of this study was to evaluate the efficacy and safety of ASCT for newly diagnosed PCNSL by means of a meta-analysis.MethodsThe PubMed, Embase, and Cochrane Library databases were systematically searched for studies published until May 20, 2021. Included studies were prospective studies of patients with newly diagnosed PCNSL treated with ASCT. The pooled rates and 95% confidence intervals (CIs) were determined for all outcomes. Subgroup analysis was conducted to compare the relative risk (RR) with 95% CIs for the complete remission (CR) rate and the hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS).ResultsThirteen prospective studies including 348 patients were analyzed. The pooled CR rate, overall response rate, and relapse rate were 80% (95% CI, 71-88%, I2 = 67.06%, p = 0.00), 95% (95% CI, 87-100%, I2 = 73.65%, p= 0.00), and 19% (95% CI, 15-24%, I2 = 76.18%, p = 0.00), respectively. The pooled 2- and 5-year PFS and OS rates were 74% (95% CI, 68-80%, I2 = 3.90%), 65% (95% CI, 51-77%, I2 = 74.61%), 80% (95% CI, 72-88%, I2 = 57.54%), and 69% (95% CI, 53-83%, I2 = 83.89%), respectively. Hematological toxicity and infections were more common adverse events above grade 3. The pooled treatment-related mortality was 3% (95% CI, 1-6%, I2 = 28.18%, p = 0.16). In the group analysis of ASCT compared with whole-brain radiotherapy, there were no significant differences in the CR rate (RR, 1.00, 95% CI, 0.88-1.14, p = 0.971), relapse rate (RR, 0.44, 95% CI, 0.06-3.10, p = 0.408), PFS (HR, 1.28, 95% CI, 0.81-2.01, p = 0.29), or OS (HR, 1.62, 95% CI, 0.97-2.69, p = 0.06). Cognitive functions were preserved or improved after ASCT.ConclusionsASCT is a feasible approach for consolidation with good tolerability for newly diagnosed PCNSL patients. High-quality randomized controlled trials are still needed to confirm the effects of ASCT.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021268422.