RESUMO
In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune-related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2-8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9-80.4), the complete response (CR) rate was 38% (95% CI, 29.3-47.3), and the median DOR was 16.4 months (95% CI, 9.5-not reached). With a median follow-up of 14.3 months (range, 1-30.5), the median progression-free survival was 11.6 months (95% CI, 8.3-not reached). Twenty-one patients (17%) discontinued therapy due to an adverse event. Grade 3-4 class-related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non-infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class-related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B-cell malignancies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Lenalidomida , Linfoma de Célula do Manto , Neoplasia Residual , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/terapia , Linfoma de Célula do Manto/patologia , Lenalidomida/uso terapêutico , Lenalidomida/administração & dosagem , Neoplasia Residual/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Talidomida/administração & dosagem , Imunoterapia/métodosRESUMO
The combination of the phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor zandelisib with the Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single-agent therapy. This phase 1 study (NCT02914938) included a dose-finding stage in patients with relapsed/refractory (R/R) B-cell malignancies (n = 20) and disease-specific expansion cohorts in follicular lymphoma (FL; n = 31) or mantle cell lymphoma (MCL; n = 19). The recommended phase 2 dose was zandelisib 60 mg on Days 1-7 plus zanubrutinib 80 mg twice daily continuously in 28-day cycle. In the total population, the most common adverse events (AEs; all grades/grade 3-4) were neutropenia (35%/24%), diarrhoea (33%/2%), thrombocytopenia (32%/8%), anaemia (27%/8%), increased creatinine (25%/0%), contusion (21%/0%), fatigue (21%/2%), nausea (21%/2%) and increased aspartate aminotransferase (24%/6%). Three patients discontinued due to AEs. The overall response rate was 87% (complete response [CR] = 33%) for FL and 74% (CR = 47%) for MCL. The median duration of response and progression-free survival (PFS) were not reached in either group. The estimated 1-year PFS was 72.3% (95% confidence interval [CI], 51.9-85.1) for FL and 56.3% (95% CI, 28.9-76.7) for MCL (median follow-up: 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Folicular , Linfoma de Célula do Manto , Pirazóis , Pirimidinas , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/mortalidade , Pirimidinas/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Pirazóis/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Adulto , Tiazóis/efeitos adversos , Tiazóis/administração & dosagem , Tiazóis/uso terapêutico , Idoso de 80 Anos ou mais , Tirosina Quinase da Agamaglobulinemia/antagonistas & inibidores , Resultado do Tratamento , PiperidinasRESUMO
Increasing use of covalent and noncovalent inhibitors of Bruton's tyrosine kinase (BTK) has elucidated a series of acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance mutations in BTK with distinct enzymatic activities, including some that impair BTK enzymatic activity while imparting novel protein-protein interactions that sustain B cell receptor (BCR) signaling. Furthermore, we describe a clinical-stage BTK and IKZF1/3 degrader, NX-2127, that can bind and proteasomally degrade each mutant BTK proteoform, resulting in potent blockade of BCR signaling. Treatment of chronic lymphocytic leukemia with NX-2127 achieves >80% degradation of BTK in patients and demonstrates proof-of-concept therapeutic benefit. These data reveal an oncogenic scaffold function of mutant BTK that confers resistance across clinically approved BTK inhibitors but is overcome by BTK degradation in patients.
Assuntos
Tirosina Quinase da Agamaglobulinemia , Resistencia a Medicamentos Antineoplásicos , Fator de Transcrição Ikaros , Leucemia Linfocítica Crônica de Células B , Inibidores de Proteínas Quinases , Proteólise , Humanos , Tirosina Quinase da Agamaglobulinemia/genética , Tirosina Quinase da Agamaglobulinemia/metabolismo , Fator de Transcrição Ikaros/metabolismo , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais , Proteólise/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacosRESUMO
This dose-finding study evaluated safety of venetoclax plus Bendamustine-Rituximab-Ibrutinib in relapsed/refractory MCL. Six 28-day cycles were administered in a 3 + 3 dose-escalation design. Dose level 1 (DL1) included Bendamustine 90 mg/m2 on day 1-2, Rituximab 375 mg/m2 on day 1, and Ibrutinib 560 mg daily. Venetoclax was dosed with ramp-up and at 400 mg starting in Cycle 2 for 5 days. The most common adverse events were thrombocytopenia (80%), constipation (60%), and fatigue (60%). Rare hematologic grade 3-4 AEs, 1 dose-limiting toxicity at DL1 (prolonged grade 3 thrombocytopenia), and delayed hematologic toxicity were observed. DL-1 with Bendamustine dose-reduced to 70 mg/m2 (n = 3) revealed no significant toxicity. The overall and complete response rates were both 80% (8/10). This study underscored that venetoclax combined with chemoimmunotherapy is complicated by hematologic toxicity, limiting future development. Although a maximum tolerated dose was not formally established given early study closure, this study demonstrated preliminary tolerability and efficacy of Bendamustine-Rituximab-Ibrutinib-Venetoclax at DL-1.
Assuntos
Adenina/análogos & derivados , Compostos Bicíclicos Heterocíclicos com Pontes , Linfoma de Célula do Manto , Piperidinas , Sulfonamidas , Trombocitopenia , Humanos , Adulto , Rituximab , Cloridrato de BendamustinaRESUMO
ABSTRACT: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard-of-care for patients with advanced-stage diffuse large B-cell lymphoma (DLBCL), despite findings that patients with nongerminal center B-cell like (non-GCB) have significantly worse outcome with this regimen. We evaluated the prognostic significance of baseline risk factors, including cell of origin (COO) classified by the Hans algorithm, within an alternative chemoimmunotherapy program. At Memorial Sloan Kettering Cancer Center (MSK), 151 patients with DLBCL received sequential R-CHOP induction and (R)-ICE (rituximab, ifosfamide, carboplatin, and etoposide) consolidation. Outcome analysis based on COO was validated with a propensity score-matched cohort treated with R-CHOP from the Mayo Clinic component of the Molecular Epidemiology Resource (MER). Among the patients with GCB (n = 69) and non-GCB (n = 69) at MSK, event-free survival (EFS) of non-GCB was superior to that of GCB (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.29-0.98). Overall survival (OS) demonstrated an association in the same direction but was not statistically significant (HR, 0.68; 95% CI, 0.33-1.42). Propensity score-matched patients from MSK (n = 108) demonstrated a small attenuation in the HRs for EFS (HR, 0.57; 95% CI, 0.27-1.18) and OS (HR, 0.76; 95% CI, 0.33-1.79) and were no longer statistically significant. In contrast, the matched MER cohort (n = 108) demonstrated an EFS association (HR, 1.17; 95% CI, 0.70-1.95) and OS association (HR, 1.13; 95% CI, 0.64-2.00) in the opposite direction, but were also not statistically significant. R-CHOP induction and (R)-ICE consolidation may overcome the negative prognostic impact of the non-GCB phenotype, per the Hans algorithm, and can be preferentially selected for this population. This trial was registered at www.ClinicalTrials.gov as #NCT00039195 and #NCT00712582.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Doxorrubicina , Ifosfamida , Linfoma Difuso de Grandes Células B , Prednisona , Rituximab , Vincristina , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Ifosfamida/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Prednisona/uso terapêutico , Prognóstico , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico , Estudos de Casos e ControlesAssuntos
Doença de Hodgkin , Linfoma não Hodgkin , Humanos , Doença de Hodgkin/tratamento farmacológico , Gencitabina , Anticorpos Monoclonais Humanizados/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Recidiva Local de NeoplasiaRESUMO
Chemoimmunotherapy followed by consolidative high-dose therapy with autologous stem cell rescue was a standard upfront treatment for fit patients with mantle cell lymphoma (MCL) in first remission; however, treatment paradigms are evolving in the era of novel therapies. Lenalidomide is an immunomodulatory agent with known efficacy in treating MCL. We conducted a single-center, investigator-initiated, phase II study of immunochemotherapy incorporating lenalidomide, without autologous stem cell transplant consolidation, enriching for patients with high-risk MCL (clinicaltrials gov. Identifier: NCT02633137). Patients received four cycles of lenalidomide-R-CHOP, two cycles of R-HiDAC, and six cycles of R-lenalidomide. The primary endpoint was rate of 3-year progression-free survival. We measured measurable residual disease (MRD) using a next-generation sequencing-based assay after each phase of treatment and at 6 months following end-oftreatment. We enrolled 49 patients of which 47 were response evaluable. By intent-to-treat, rates of overall and complete response were equivalent at 88% (43/49), one patient with stable disease, and two patients had disease progression during study; 3-year progression-free survival was 63% (primary endpoint not met) and differed by TP53 status (78% wild-type vs. 38% ALT; P=0.043). MRD status was prognostic and predicted long-term outcomes following R-HiDAC and at 6 months following end-of-treatment. In a high-dose therapy-sparing, intensive approach, we achieved favorable outcomes in TP53- wild-type MCL, including high-risk cases. We confirmed that sequential MRD assessment is a powerful prognostic tool in patients with MCL.
Assuntos
Linfoma de Célula do Manto , Adulto , Humanos , Lenalidomida/uso terapêutico , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Prognóstico , ImunoterapiaRESUMO
Novel targeted therapies (small molecule inhibitors, antibody-drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton's tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.
Assuntos
Linfoma Folicular , Linfoma Difuso de Grandes Células B , Linfoma de Célula do Manto , Humanos , Adulto , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Folicular/tratamento farmacológico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Imunoterapia Adotiva , Linfócitos TAssuntos
Antineoplásicos , Linfoma de Células B , Linfoma não Hodgkin , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Fosfatidilinositol 3-Quinases , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêuticoRESUMO
Nodal marginal zone lymphoma (NMZL) is a rare non-Hodgkin B-cell lymphoma that has historically been difficult to define, though is now formally recognized by the World Health Organization Classification. To better characterize the clinical outcomes of patients with NMZL, we reviewed a sequential cohort of 187 patients with NMZL to describe baseline characteristics, survival outcomes, and time-to-event data. Initial management strategies were classified into five categories: observation, radiation, anti-CD20 monoclonal antibody therapy, chemoimmunotherapy, or other. Baseline Follicular Lymphoma International Prognostic Index scores were calculated to evaluate prognosis. A total of 187 patients were analyzed. The five-year overall survival was 91% (95% confidence interval [CI], 87-95), with a median follow-up time of 71 months (range, 8-253) among survivors. A total of 139 patients received active treatment at any point, with a median follow-up time of 56 months (range, 13-253) among survivors who were never treated. The probability of remaining untreated at five years was 25% (95% CI, 19-33). For those initially observed, the median time to active treatment was 72 months (95% CI, 49-not reached). For those who received at least one active treatment, the cumulative incidence of receiving a second active treatment at 60 months was 37%. Transformation to large B-cell lymphoma was rare, with a cumulative incidence of 15% at 10 years. In summary, our series is a large cohort of uniformly diagnosed NMZL with detailed analyses of survival and time to event analyses. We showed that NMZL commonly presents as an indolent lymphoma for which initial observation is often a reasonable strategy.
Assuntos
Antineoplásicos , Linfoma de Zona Marginal Tipo Células B , Humanos , Estudos Retrospectivos , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Prognóstico , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/uso terapêuticoRESUMO
PURPOSE: Pirtobrutinib is a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor (BTKi). We report the safety and efficacy of pirtobrutinib in patients with covalent Bruton tyrosine kinase inhibitor (cBTKi) pretreated mantle-cell lymphoma (MCL), a population with poor prognosis. METHODS: Patients with cBTKi pretreated relapsed/refractory (R/R) MCL received pirtobrutinib monotherapy in a multicenter phase I/II trial (BRUIN; ClinicalTrials.gov identifier: NCT03740529). Efficacy was assessed in the first 90 consecutively enrolled patients who met criteria for inclusion in the primary efficacy cohort. The primary end point was overall response rate (ORR). Secondary end points included duration of response (DOR) and safety. RESULTS: The median patient age was 70 years (range, 46-87), the median prior lines of therapy was 3 (range, 1-8), 82.2% had discontinued a prior cBTKi because of disease progression, and 77.8% had intermediate- or high-risk simplified MCL International Prognostic Index score. The ORR was 57.8% (95% CI, 46.9 to 68.1), including 20.0% complete responses (n = 18). At a median follow-up of 12 months, the median DOR was 21.6 months (95% CI, 7.5 to not reached). The 6- and 12-month estimated DOR rates were 73.6% and 57.1%, respectively. In the MCL safety cohort (n = 164), the most common treatment-emergent adverse events (TEAEs) were fatigue (29.9%), diarrhea (21.3%), and dyspnea (16.5%). Grade ≥3 TEAEs of hemorrhage (3.7%) and atrial fibrillation/flutter (1.2%) were less common. Only 3% of patients discontinued pirtobrutinib because of a treatment-related adverse event. CONCLUSION: Pirtobrutinib is a first-in-class novel noncovalent (reversible) BTKi and the first BTKi of any kind to demonstrate durable efficacy after prior cBTKi therapy in heavily pretreated R/R MCL. Pirtobrutinib was well tolerated with low rates of treatment discontinuation because of toxicity.
Assuntos
Linfoma de Célula do Manto , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
Nodal peripheral T-cell lymphomas (PTCL), the most common PTCLs, are generally treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based curative-intent chemotherapy. Recent molecular data have assisted in prognosticating these PTCLs, but most reports lack detailed baseline clinical characteristics and treatment courses. We retrospectively evaluated cases of PTCL treated with CHOP-based chemotherapy that had tumors sequenced by the Memorial Sloan Kettering Integrated Mutational Profiling of Actionable Cancer Targets next-generation sequencing panel to identify variables correlating with inferior survival. We identified 132 patients who met these criteria. Clinical factors correlating with an increased risk of progression (by multivariate analysis) included advanced-stage disease and bone marrow involvement. The only somatic genetic aberrancies correlating with inferior progression-free survival (PFS) were TP53 mutations and TP53/17p deletions. PFS remained inferior when stratifying by TP53 mutation status, with a median PFS of 4.5 months for PTCL with a TP53 mutation (n = 21) vs 10.5 months for PTCL without a TP53 mutation (n = 111). No TP53 aberrancy correlated with inferior overall survival (OS). Although rare (n = 9), CDKN2A-deleted PTCL correlated with inferior OS, with a median of 17.6 months vs 56.7 months for patients without CDKN2A deletions. This retrospective study suggests that patients with PTCL with TP53 mutations experience inferior PFS when treated with curative-intent chemotherapy, warranting prospective confirmation.
Assuntos
Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/genética , Prognóstico , Estudos Retrospectivos , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , MutaçãoRESUMO
Recent prospective clinical trial data suggest that patients with Hodgkin's lymphoma who continue treatment with ABVD, despite failing to attain a complete metabolic response on interim PET (PET2+), may fare better than previously published. We describe the outcomes of PET2+ patients who continued ABVD and compare the performance of a quantitative measure based on the lesion-to-liver SUV ratio (LLS qPET2+) to that of the subjective Deauville criteria (dvPET2+). We analyzed all patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with frontline ABVD at the Memorial Sloan Kettering Cancer Center between 2008 and 2017. Eligibility was set to correspond with the RATHL inclusion criteria. Images were reviewed by two nuclear medicine physicians and discordant cases were resolved with a third expert in consensus. qPET2+ was defined as LLS ≥ 1.3. We identified 227 patients of whom 25% (57) were qPET2+, but only 14% (31) were dvPET2+. Forty-eight patients (84%) continued ABVD with a 3-year PFS of 70% for qPET2+ and 64% for dvPET2+. In conclusion, interim PET interpretation in clinical practice may be associated with a higher rate of scans deemed positive. Irrespective of the criteria for PET2 positivity, a subset of patients may continue ABVD without a dismal outcome.
Assuntos
Linfoma não Hodgkin , Recidiva Local de Neoplasia , Humanos , Proteína de Ligação a CREB/genética , Proteína p300 Associada a E1A/genética , Epigênese Genética , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/genética , Mutação , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genéticaRESUMO
While most patients with follicular lymphoma (FL) have excellent outcomes with frontline chemoimmunotherapy (CIT), a subset of patients will experience early progression, which is associated with poor subsequent outcomes. Novel biomarkers are needed to identify high-risk patients earlier. We hypothesized that interim positron emission tomography (PET) would predict progression-free survival (PFS) in this population. We retrospectively identified 128 patients with grade 1-3A FL who had an interim PET after 2-4 cycles of frontline CIT at 2 academic centers. PET scans were analyzed using Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Interim PET DS was a significant predictor of PFS (P < 0.003). Patients with a DS of 3 had outcomes similar to those of patients with a DS of 4, so were categorized as PET-positive for additional analyses. Interim PET remained a strong predictor of PFS (DS 3-5, hazard ratio [HR] 2.4, P = 0.006) in a multivariable analysis and was also an early predictor of both a positive end-of-treatment PET (P < 0.001) and progression of disease within 24 months (POD24) (P = 0.006). An optimal ΔSUVmax cutoff of 75% was selected using the bootstrap method. ΔSUVmax <75% was also a significant predictor of PFS on univariable and multivariable analyses (HR 2.8, P < 0.003). In a separate cohort of 50 patients with high-grade FL, interim PET interpreted using either DS (P < 0.001) or ΔSUVmax75% (P = 0.034) was also a significant predictor of inferior PFS. In conclusion, interim PET is an independent predictor of PFS and may be useful as a tool for response-adapted treatment strategies in FL.
RESUMO
Early identification of patients with diffuse large B-cell lymphoma (DLBCL) who are likely to experience disease recurrence or refractory disease after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) would be useful for improving risk-adapted treatment strategies. We aimed to assess the prognostic value of 18F-FDG PET/CT parameters at baseline, interim, and end of treatment (EOT). Methods: We analyzed the prognostic impact of 18F-FDG PET/CT in 166 patients with DLBCL treated with a risk-adapted immunochemotherapy regimen. Scans were obtained at baseline, after 4 cycles of R-CHOP or 3 cycles of RR-CHOP (double dose of R) and 1 cycle of CHOP alone (interim) and 6 wk after completing therapy (EOT). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier and the impact of clinical/PET factors assessed with Cox models. We also assessed the predictive ability of the recently proposed International Metabolic Prognostic Index (IMPI). Results: The median follow-up was 7.9 y. International Prognostic Index (IPI), baseline metabolic tumor volume (MTV), and change in maximum SUV (ΔSUVmax) at interim scans were statistically significant predictors for OS. Baseline MTV, interim ΔSUVmax, and EOT Deauville score were statistically significant predictors of PFS. Combining interim PET parameters demonstrated that patients with Deauville 4-5 and positive ΔSUVmax ≤ 70% at restaging (â¼10% of the cohort) had extremely poor prognosis. The IMPI had limited discrimination and slightly overestimated the event rate in our cohort. Conclusion: Baseline MTV and interim ΔSUVmax predicted both PFS and OS with this sequential immunochemotherapy program. Combining interim Deauville score with interim ΔSUVmax may identify an extremely high-risk DLBCL population.
Assuntos
Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Prognóstico , Fluordesoxiglucose F18/uso terapêutico , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/uso terapêutico , Ciclofosfamida/uso terapêutico , Vincristina/uso terapêutico , Prednisona/uso terapêutico , Doxorrubicina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos RetrospectivosRESUMO
Targeted therapies have largely replaced chemoimmunotherapy (CIT) in first-line treatment of chronic lymphocytic leukemia (CLL). We aimed to develop a prognostic model to determine who would benefit from first-line CIT vs target therapy. In follicular lymphoma, time from diagnosis to second treatment (TT2T) correlates better with overall survival (OS) than time from diagnosis to first treatment (TT1T). We hypothesized that TT2T is a potential surrogate for OS in CLL. In a model-building cohort (n = 298), we evaluated potential predictors for TT2T and derived a risk score, which we validated in an external cohort (n = 1141). Our data demonstrated that TT2T and OS were more strongly correlated than TT1T and OS. Our risk score model consisted of three predictors (unmutated IGHV, ß2-microglobulin >297 nmol/L, and Rai stage I-IV), and was prognostic for TT2T and OS. TT2T is a promising surrogate for OS in CLL, but further validation is needed to establish this association.