RESUMEN
Burkitt lymphoma (BL) is a rare subtype of non-Hodgkin's lymphoma with an aggressive course. To refine the individual patient's prognosis, the International Prognostic Index for BL (BL-IPI) was recently developed and 4 risk factors (RF) were determined as optimal prognostic cut-off by multivariate analysis: age ≥40 years, lactate dehydrogenase >3× upper limit of normal, ECOG performance status ≥2, and central nervous system involvement. The BL-IPI distinguishes 3 prognostic groups, low (without RF), intermediate (1 RF), and high risk (2-4 RF), with significant differences in survival. The aim of the current project was to perform an external validation of the BL-IPI in 101 patients from the Registry of Czech Lymphoma Study Group diagnosed between 1999 and 2016 (median age, 45 years). The median follow-up was 50.4 months. The induction treatment included rituximab plus chemotherapy in 82% and chemotherapy alone in 18%. The overall response rate was 78% and the complete remission rate was 73%. According to BL-IPI, low/intermediate/high risk was present in 21/35/45% of patients, showing high similarity to the training BL-IPI US (United States) dataset (18/36/46%). There were significant differences in progression-free survival (PFS) and overall survival (OS) between patients with high vs. intermediate risk (PFS: hazard ratio 0.16, 95% confidence interval 0.08-0.31, p<0.0001; OS: hazard ratio 0.17, 95% confidence interval 0.09-0.35, p<0.0001) but not between patients with low vs. intermediate risk. The 3-year OS probability according to BL-IPI with low/intermediate/high risk was 96/76/59% in the BL-IPI training dataset vs. 95/85/45% in our external validation cohort; the 3-year PFS probability with low/intermediate/high risk was 92/72/53% in the BL-IPI training dataset vs. 95/85/42% in our cohort. In summary, our external validation of the BL-IPI confirmed a good separation of high-risk patients, who have a poor prognosis and for whom the new therapeutic approaches are needed; patients with low and intermediate risk had favorable clinical outcomes, and differences between these groups were not significant, likely due to a small number of patients.
Asunto(s)
Linfoma de Burkitt , Linfoma de Células B Grandes Difuso , Humanos , Persona de Mediana Edad , Adulto , Linfoma de Burkitt/tratamiento farmacológico , Pronóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Estudios Retrospectivos , República Checa/epidemiología , Sistema de Registros , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Rituximab maintenance (RM) prolongs survival of elderly patients with mantle cell lymphoma (MCL). Persistent minimal residual disease (MRD) after induction repeatedly correlated with shorter progression-free survival (PFS). However, none of the published studies analyzed patients treated with RM. The main purpose was to analyze prognostic significance of MRD in the elderly patients with newly diagnosed MCL treated according to the recently published observational trial protocol (alternation of R-CHOP and R-cytarabine, 3 + 3 cycles, GovTrial number NCT03054883) at the centers that implemented RM. Minimal residual disease was evaluated by a EuroMRD standardized real-time PCR approach after 3 and 6 cycles of the induction therapy. Prognostic significance of MRD was analyzed in a subcohort of patients treated at the centers that implemented RM as a standard approach. Bone marrow proved to be a significantly more sensitive source for MRD detection than peripheral blood. In either compartment MRD (positive versus negative) after 3 or 6 cycles of the induction therapy did not correlate with PFS. The observed loss of prognostic significance of MRD after the R-CHOP-based induction appears to be a consequence of RM immune control over the residual lymphoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma de Células del Manto , Quimioterapia de Mantención , Rituximab/administración & dosificación , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma de Células del Manto/sangre , Linfoma de Células del Manto/tratamiento farmacológico , Linfoma de Células del Manto/mortalidad , Masculino , Persona de Mediana Edad , Neoplasia Residual , Prednisona/administración & dosificación , Tasa de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
Implementation of cytarabine into induction therapy became standard of care for younger patients with mantle cell lymphoma (MCL). On the basis of its beneficial impact, many centers incorporated cytarabine at lower doses also into first-line treatments of elderly patients. We conducted a multicenter observational study that prospectively analyzed safety and efficacy of alternating 3 + 3 cycles of R-CHOP and R-cytarabine for newly diagnosed transplant-ineligible MCL patients. A total of 73 patients were enrolled with median age 70 years. Most patients had intermediate (39.7%) and high-risk (50.7%) disease according to MCL international prognostic index. Rituximab maintenance was initiated in 58 patients. Overall response rate reached 89% by positron emission tomography-computed tomography, including 75.3% complete remissions. Two patients (2.7%) did not complete the induction therapy because of toxicity. Three patients (4.1%) were considered nonresponders, which led to therapy change before completion of induction. Estimated progression-free survival and overall survival were 51.3% and 68.6% at 4 years, respectively. Mantle cell lymphoma international prognostic index, bulky disease (≥ 5 cm), and achievement of positron emission tomography-negativity independently correlated with progression-free survival. Grade 3 to 4 hematologic and nonhematologic toxicity was documented in 48% and 20.5% patients, respectively. Alternation of R-CHOP and R-cytarabine represents feasible and very effective regimen for elderly/comorbid MCL patients. This study was registered at GovTrial (clinicaltrials.gov) NCT03054883.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Citarabina/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/farmacología , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Ciclofosfamida/farmacología , Ciclofosfamida/uso terapéutico , Citarabina/farmacología , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Femenino , Humanos , Linfoma de Células del Manto/patología , Masculino , Persona de Mediana Edad , Prednisona/farmacología , Prednisona/uso terapéutico , Rituximab , Vincristina/farmacología , Vincristina/uso terapéuticoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/terapia , Rituximab/uso terapéutico , Adulto , Anciano , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Linfoma de Células del Manto/mortalidad , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Inducción de Remisión/métodos , Análisis de Supervivencia , Trasplante AutólogoRESUMEN
Mantle cell lymphoma (MCL) is a subtype of B-cell lymphoma with a large number of recurrent cytogenetic/molecular aberrations. Approximately 5-10% of patients do not respond to frontline immunochemotherapy. Despite many useful prognostic indexes, a reliable marker of chemoresistance is not available. We evaluated the prognostic impact of seven recurrent gene aberrations including tumor suppressor protein P53 (TP53) and cyclin dependent kinase inhibitor 2A (CDKN2A) in the cohort of 126 newly diagnosed consecutive MCL patients with bone marrow involvement ≥5% using fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS). In contrast to TP53, no pathologic mutations of CDKN2A were detected by NGS. CDKN2A deletions were found exclusively in the context of other gene aberrations suggesting it represents a later event (after translocation t(11;14) and aberrations of TP53, or ataxia telangiectasia mutated (ATM)). Concurrent deletion of CDKN2A and aberration of TP53 (deletion and/or mutation) represented the most significant predictor of short EFS (median 3 months) and OS (median 10 months). Concurrent aberration of TP53 and CDKN2A is a new, simple, and relevant index of chemoresistance in MCL. Patients with concurrent aberration of TP53 and CDKN2A should be offered innovative anti-lymphoma therapy and upfront consolidation with allogeneic stem cell transplantation.
RESUMEN
The rituximab maintenance (RM) therapy for follicular lymphoma is effective and clinically well tolerated, however there is limited data regarding this from the elderly segment of the population. This analysis was performed to evaluate the efficacy of RM in elderly patients 65 years of age and older and to assess the influence of the induction therapy with immunochemotherapy (R-CHEMO) on the treatment outcome in a real world setting. A total of 232 consecutive patients treated with first-line R-CHEMO and RM (RM1 group; n = 158) or observation (RM0 group; n = 74) were analyzed. The effect of which induction therapy (R-CHOP vs. R-CVP) and the response of the patients to the first-line therapy were also evaluated. The addition of RM improved the treatment results in elderly patients. The 5- year overall survival rate in patients receiving R-CHEMO + RM1 compared to patients receiving R-CHEMO + RM0, was 83.7% (95% CI 76.1-89%) and 64.3% (95% CI 51.8-74.3%), respectively, p = 0.0012. The induction therapy with R-CHOP was found to be more effective than R-CVP but it is necessary to point out higher age of patients in the R-CVP arm. The 5- year overall survival rate in patients using R-CHOP ± RM and R-CVP ± RM was 84.9% (95% CI 77.5-90%), and 65.0% (95% CI 50.1-76.4%), respectively, p = 0.0008. The patients who achieved CR + uCR after having received first-line therapy had better outcomes compared to patients in PR. The 5- year overall survival rate in uCR + CR patients treated with R-CHEMO + RM1 and PR patients treated with R-CHEMO + RM1 was 90.6% and 68.3%, respectively, p = 0.0019. Rituximab maintenance treatment in patients 65 years and older yielded improved survival rates in a real world clinical setting. The R-CHOP regimen seems to be a more effective induction agent than R-CVP but the outcome of less intensively treated patients with R-CVP + RM is also acceptable. The achievement of uCR + CR after first-line therapy is associated with a better outcome.