Genomic landscape of comprehensive genomic profiling in patients with malignant solid tumors in Japan.

BACKGROUND: Comprehensive genomic profiling (CGP) can aid the discovery of clinically useful, candidate antitumor agents; however, the variant annotations sometimes differ among the various types of CGP tests as well as the public database. The aim of this study is to clarify the genomic landscape of evaluating detected variants in patients with a malignant solid tumor. METHODS: The present, cross-sectional study used data from 57,084 patients with a malignant solid tumor who underwent CGP at the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 1, 2019 and August 18, 2023. The pathogenicity of the variants was annotated using public databases. RESULTS: As a result of re-annotation of the detected variants, 20.1% were pathogenic and 1.4% were benign. The mean number of pathogenic variants was 4.30 (95% confidence interval: 4.27-4.32) per patient. Of the entire cohort, 5.7% had no pathogenic variant. The co-occurrence of the genes depended on the tumor type. Germline findings were detected in 6.2%, 8.8%, and 15.8% of the patients using a tumor/normal panel, tumor-only panel, and liquid panel, respectively, with the most common gene being BRCA2 followed by TP53 and BRCA1. CONCLUSIONS: The detected variants should be re-annotated because several benign variants or variants of unknown significance were included in the CGP, and the genomic landscape derived from these results will help researchers and physicians interpret the results of CGP tests. The method of extracting presumptive, germline, pathogenic variants from patients using a tumor-only panel or circulating tumor DNA panel requires improvement.

Selection bias due to delayed comprehensive genomic profiling in Japan.

Patients with advanced cancer undergo comprehensive genomic profiling in Japan only after treatment options have been exhausted. Patients with a very poor prognosis were not able to undergo profiling tests, resulting in a selection bias called length bias, which makes accurate survival analysis impossible. The actual impact of length bias on the overall survival of patients who have undergone profiling tests is unclear, yet appropriate methods for adjusting for length bias have not been developed. To assess the length bias in overall survival, we established a simulation-based model for length bias adjustment. This study utilized clinicogenomic data of 8813 patients with advanced cancer who underwent profiling tests at hospitals throughout Japan between June 2019 and April 2022. Length bias was estimated by the conditional Kendall τ statistics and was significantly positive for 13 of the 15 cancer subtypes, suggesting a worse prognosis for patients who underwent profiling tests in early timing. The median overall survival time in colorectal, breast, and pancreatic cancer from the initial survival-prolonging chemotherapy with adjustment for length bias was 937 (886-991), 1225 (1152-1368), and 585 (553-617) days, respectively (median; 95% credible interval). Adjusting for length bias made it possible to analyze the prognostic relevance of oncogenic mutations and treatments. In total, 12 tumor-specific oncogenic mutations correlating with poor survival were detected after adjustment. There was no difference in survival between FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) or gemcitabine with nab-paclitaxel-treated groups as first-line chemotherapy for pancreatic cancer. Adjusting for length bias is an essential part of utilizing real-world clinicogenomic data.

Utility of the frailty score for predicting prognosis and individualizing treatment intensity in elderly patients with diffuse large B cell lymphoma.

The optimal dose intensity of chemotherapy for elderly patients with diffuse large B cell lymphoma (DLBCL) remains controversial because of concerns about adverse events and comorbidities related to the patients' frailty. This single-center study retrospectively analyzed patients aged ≥ 70 years who were newly diagnosed with DLBCL and received chemotherapy between 2004 and 2022. Survival outcomes and treatment-related mortality (TRM) were stratified according to geriatric assessment variables, and the influence of chemotherapy dose intensity on outcomes was assessed using the frailty score with a Cox hazards model with restricted cubic spline (RCS) in patients aged 70-79 years. In total, 337 patients were included. The frailty score accurately predicted prognosis (5-year overall survival [OS]: 73.1%, 60.2%, and 29.7% in fit, unfit, and frail patients, respectively; P < 0.001) and TRM (5-year TRM: 0%, 5.4%, and 16.8 in fit, unfit, and frail patients, respectively; P < 0.001). Cox regression with RCS demonstrated a linear association between dose intensity and survival outcomes. Initial dose intensity (IDI) and relative dose intensity (RDI) had a significant impact on OS in fit patients. However, IDI and RDI had no significant effect on survival in non-fit (unfit and frail) patients. The frailty score identified non-fit patients with poorer survival and a higher risk of TRM. While fit patients were likely to benefit from full-dose R-CHOP, unfit and frail patients would likely benefit more from attenuated R-CHOP. This study suggested a potential role for the frailty score in individualizing treatment intensity in elderly patients with DLBCL.

[Polatuzumab vedotin, bendamustine, and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma, including the outcome as a bridging treatment to CAR-T cell therapy or allogeneic hematopoietic stem cell transplant].

Pola-BR (polatuzumab vedotin, bendamustine, and rituximab) therapy received approval for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in Japan in March 2021. There have been few reports on the efficacy and safety of Pola-BR therapy in Japanese clinical practice. A retrospective analysis was performed on twenty-nine patients with R/R DLBCL who received Pola-BR therapy at our institution (intent to cellular immunotherapy cohort: 20 patients, stand-alone treatment cohort: nine patients). The overall response rate was 69.0% (complete response 27.6%). The median progression-free survival was 5.1 months, with a 9.5-month median overall survival. In the intent to cellular immunotherapy cohort, 11 of 19 patients received chimeric antigen receptor T-cell (CAR-T) infusions, and one patient received allogeneic stem cell transplantation. Four patients received Pola-BR therapy, including bendamustine before leukapheresis, and all produced CAR-T products successfully. 3 of the 28 patients experienced grade3 or higher adverse events, and two required treatment discontinuation. Our single institution, a real-world cohort of R/R DLBCL patients showed high efficacy outcomes and a tolerable toxicity profile for Pola-BR therapy, which is comparable to previous studies. More cases are needed to determine its impact on CAR-T therapy and stem cell transplantation.

Synchronous multiple primary tumors in patients with malignant lymphoma: a retrospective study.

BACKGROUND: Synchronous multiple primary malignant tumors (sMPMTs) are sometimes diagnosed in patients with malignant lymphoma. We herein investigated the prognostic impact of sMPMT in lymphoma patients and the optimal treatment strategy. METHODS: Seventy-five patients with sMPMTs (5.8%) among 1285 patients with lymphoma newly diagnosed between August 2004 and April 2020 were enrolled. RESULTS: In patients with indolent lymphoma, those with sMPMTs had a worse prognosis than those without sMPMTs (5-year overall survival [OS]: 73.4% and 87.8%, respectively; P = 0.047). Among those with high and low tumor burden, the cumulative rate of death due to solid tumors was significantly higher in patients with sMPMTs than those without sMPMTs (high tumor burden: 26.7% vs. 1.6%, P < 0.001; low tumor burden: 12.7% vs. 1.0%, P = 0.003). The presence of sMPMTs did not have a significant impact on outcomes in patients with diffuse large B-cell lymphoma (DLBCL) (5-year OS: 65.4% and 66.9%, respectively; P = 0.74; 5-year progression-free survival [PFS]: 65.5% and 59.9%, respectively; P = 0.65). However, the cumulative rate of death from solid tumor in patients with sMPMTs was significantly higher than in patients without sMPMTs (5-year cumulative rate: 7.4% and 2.1%, respectively; P = 0.004). The treatment sequence did not have a significant effect on outcomes or the relative dose intensity of chemotherapy. CONCLUSIONS: In patients with indolent lymphoma, those with sMPMTs had a significantly worse prognosis than those without sMPMTs, mainly because of high mortality due to solid tumors. The presence of sMPMTs was not a significant prognostic factor in patients with DLBCL. It is important to assess the status and need for early treatment of each type of malignancy in patients with sMPMTs.

[Tisagenlecleucel for relapsed/refractory diffuse large B-cell lymphoma: real-world data from single institute experience].

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the approach to patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study retrospectively analyzed patients treated with commercially available tisagenlecleucel at our hospital and evaluated its safety and effectiveness. Of the 21 patients evaluated, any grade and grade ≥3 cytokine release syndrome (CRS) occurred in 85.7% and 9.5% of the patients, respectively. A total of 66.7% received tocilizumab and 28.6% received glucocorticoids for the treatment of CRS. The complete response (CR) rate at 3 months was 61.9% (95% confidence interval [CI] 38.4-81.9). After a median follow-up of 6.3 months following CAR-T infusion, the progression-free survival (PFS) and overall survival rates at 6 months were 53.1% (95%CI 28.3-72.7) and 69.2% (95%CI 43.7-84.9), respectively. Severe cytopenia and hypogammaglobulinemia occurred frequently following CAR-T infusion. Eight patients (38.1%) had comorbidities that would have made them ineligible for leukapheresis in the JULIET trial. However, the presence of comorbidities at the time of leukapheresis had no significant effect on the rates of CR, PFS, and adverse events. Tisagenlecleucel for r/r DLBCL in the real-world setting showed high efficacy and manageable safety profile comparable with the pivotal trial.

Characteristics and outcomes of coronavirus disease 2019 (COVID-19) patients with cancer: a single-center retrospective observational study in Tokyo, Japan.

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of coronavirus disease 2019 (COVID-19), data on the clinical characteristics of COVID-19 patients with cancer are limited. This study aimed to evaluate the clinical characteristics and outcomes including mortality and viral shedding period in COVID-19 patients with cancer in Japan. METHODS: We retrospectively analyzed 32 patients with a history of cancer who were referred to our hospital between January 31, 2020 and May 25, 2020. We evaluated the association between clinical outcomes and potential prognostic factors using univariate analyses. RESULTS: The median age was 74.5 (range 24-90) years and 22 patients (69%) were men. A total of 11 patients (34%) died. Our analyses demonstrated that the mortality was significantly associated with lymphocyte count, albumin, lactate dehydrogenase, serum ferritin, and C-reactive protein on admission. The median period between illness onset and the first effective negative SARS-CoV-2 PCR result was 22 days (interquartile range 18-25) in survivors. Of four patients with hematological malignancy who developed COVID-19 within the rest period of chemotherapy, three died and the other patient, who received bendamustine plus rituximab therapy, had the longest duration of viral shedding (56 days). CONCLUSION: Our study suggested that the risk factors for mortality previously reported in general COVID-19 patients, including lymphocytopenia, were also effective in cancer patients. Patients who received cytotoxic chemotherapy recently or were treated with chemotherapy, which can lead to lymphocyte reduction, had poor prognosis and prolonged periods of viral shedding.

Clinical impact of controlling nutritional status score on the prognosis of patients with diffuse large B-cell lymphoma.

The controlling nutritional status (CONUT) score is a nutritional index calculated from serum albumin and total cholesterol levels and lymphocyte counts. Its role in predicting clinical outcomes of diffuse large B-cell lymphoma (DLBCL) has not been evaluated. In this retrospective study, data from 476 patients with DLBCL were analyzed. The cutoff value of the CONUT score was set as 4. CONUT score significantly stratified the overall survival (OS) and the progression-free-survival (PFS) (5-year OS, 49.0% vs 83.2%, P < .001; 5-year PFS, 46.1% vs 73.1%, P < .001) of the patients. Among patients at high-intermediate or high risk, as per the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), 5-year OS was lower in patients with high CONUT scores than in those with low CONUT scores (high-intermediate risk, 51.2% vs 75.5%, P < .001; high risk, 29.9% vs 63.3%, P = .007). Additionally, in patients with high CONUT scores, maintenance of relative dose intensity (RDI) of chemotherapy did not affect the 5-year OS (RDI > 80% vs RDI ≤ 80%: 59.8% vs 50.9%, P = .73). In the present study, we have demonstrated that the CONUT score is an independent prognostic factor in patients with DLBCL.

[Clinical Efficacy of mFOLFOX6 for Advanced Gastric Cancer].

FOLFOX therapy has been used for gastric cancer in Japan since 2017. We retrospectively analyzed the efficacy of FOLFOX therapy compared to that of FP. Forty-seven cases were evaluated between January 2010 and December 2018. Eighteen patients received mFOLFOX6 therapy, and 29 patients received FP therapy. The median time to treatment failure was 206 days in the mFOLFOX6 group and 58 days in the FP group. The response rate was 50% in the mFOLFOX6 group and 17% in the FP group. Neutropenia(56%), thrombocytopenia(50%), and peripheral neuropathy(56%)were the common adverse events in the mFOLFOX6 group, and leukopenia(69%)and neutropenia(69%)were the common adverse effects in the FP group. Based on our results, we conclude that, unlike FP, FOLFOX is an effective therapy for of gastric cancer.

[Efficacy of Amrubicin Monotherapy for Patients with Extrapulmonary Neuroendocrine Carcinomas Refractory to Platinum-Based Chemotherapy].

Standard regimens for extrapulmonary neuroendocrine carcinomas(EPNEC)are not established. Treatment used for small cell lung cancer is also used for EPNECs. Amrubicin(AMR) monotherapy is used as salvage therapy for small cell lung cancer, but its efficacy in EPNEC is not clear. The aim of this study was to estimate the efficacy of AMR monotherapy in EPNEC. We retrospectively investigated patients with EPNEC who received first-line platinum-based chemotherapy between April 2007 and March 2019. The time to treatment failure(TTF)and the efficacy and toxicity was analyzed in the patients who received AMR monotherapy. Among 43 patients with EPNEC, 14(13 males, one female; median age, 58 years)received AMR monotherapy. Primary site included the pancreas(n=3), stomach(n=3), rectum(n=1), anal canal(n=1), salivary glands(n= 1), urothelial(n=1), bladder(n=1), prostate(n=1), and 2 patients had primary unknown cancer. Pathological type included small cell(n=4), large cell(n=2), and other types(n=8). Prior chemotherapy comprised CDDP plus CPT-11(n =5), CDDP plus ETP(n=2), and CBDCA plus ETP(n=6). The median TTF was 49(20-61)days. One patient had a partial response and the disease control rate was 33%. The common adverse events of >Grade 3 were leukopenia(69%), neutropenia(62%), and febrile neutropenia(23%). AMR monotherapy was clinically effective and safe for EPNEC.

Analysis of the prognostic value of BMI and the difference in its impact according to age and sex in DLBCL patients.

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B-cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R-CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (<18.5 kg/m2 ), 58 (14.3%); normal weight (≥18.5 to <25 kg/m2 ), 262 (64.5%); overweight (≥25 to <30 kg/m2 ), 75 (18.5%); and obese (≥30.0 kg/m2 ), 11 (2.7%). While the prognosis of overweight patients was good, being similar to that of normal weight, underweight, and obese patients had a worse prognosis (5-y overall survival [OS] was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight, and obese patients, respectively; P = .004). In multivariate analysis, underweight and obesity were independent prognostic factors for OS compared with normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female patients (≥70 y), patients with a low BMI (<25 kg/m2 ) had significantly inferior OS than those with a high BMI (≥25 kg/m2 ) (5-y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (<70 years), patients with a low BMI had significantly better OS than those with a high BMI (5-y OS, 88.6% vs 46.4%; P < .001). In male patients, there were no differences in the effect of BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age.

Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma.

The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI < 96.8 had significantly lower overall survival (OS) and progression-free survival (PFS) than those with a GNRI ≥ 96.8 (5-year OS, 61.2 vs. 84.4%, P < 0.001; 5-year PFS, 53.7 vs. 75.8%, P < 0.001). Multivariate analysis showed that performance status, Ann Arbor stage, serum lactate dehydrogenase, and GNRI were independent prognostic factors for OS. Among patients with high-intermediate and high-risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI < 96.8 than in those with a GNRI ≥ 96.8 (high-intermediate risk, 59.5 vs. 75.2%, P = 0.006; high risk, 37.4 vs. 64.9%, P = 0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.

Beta-2 microglobulin as a significant prognostic factor and a new risk model for patients with diffuse large B-cell lymphoma.

Previous reports have evaluated the prognostic value of serum beta-2 microglobulin (B2MG) level in patients with non-Hodgkin lymphoma. However, its role in predicting clinical outcome of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been extensively investigated. Here, we evaluated the prognostic value of B2MG and proposed a new prognostic model including B2MG for patients with DLBCL. A total of 274 patients with newly diagnosed de novo DLBCL were retrospectively analyzed. We defined the best cutoff value as 3.2 mg/L by using a receiver operating characteristic curve. Patients with a B2MG level ≥3.2 mg/L had significantly lower overall survival (OS) and progression-free survival than those with a B2MG level <3.2 mg/L (3-year OS, 50.9% vs. 89.4%, p < 0.001; 3-year progression-free survival, 45.3% vs. 79.7%, p < 0.001). Multivariate analysis showed that B2MG, age, performance status, and Ann Arbor stage were independent prognostic factors for OS. We developed a new prognostic model consisting of these four significant factors. We stratified patients into four-risk groups: low (L, 0 factor), low-intermediate (LI, 1-2 factors), high-intermediate (HI, 3 factors), high (H, 4 factors). This new prognostic model showed better risk discrimination compared with the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 100% and 23.4% vs. 100% and 27.1%, in L and H risk groups, respectively). Our study suggested that B2MG level is a significant prognostic factor in patients with DLBCL. A new prognostic index composed of age, performance status, stage, and B2MG could stratify the outcomes of patients with DLBCL effectively and appears to be a valuable risk model for these patients. Copyright © 2016 John Wiley & Sons, Ltd.

Central nervous system relapse in patients with diffuse large B cell lymphoma: analysis of the risk factors and proposal of a new prognostic model.

Central nervous system (CNS) relapse in patients with diffuse large B cell lymphoma (DLBCL) is an uncommon event, and the outcome of patients with CNS relapse is poor. However, no reliable prediction models for CNS relapse have been developed. We retrospectively analyzed consecutive de novo DLBCL patients referred to our department between September 2004 and August 2015 and treated with R-CHOP or R-CHOP-like regimens. Of 413 patients analyzed in this study, a total of 27 patients (6.5 %) eventually developed CNS relapse. The 5-year probability of CNS relapse was 8.4 %. The median time from diagnosis of DLBCL to CNS relapse was 15 months, and the median survival after CNS relapse was 7 months. In univariate analysis, the risk factors significantly associated with CNS relapse were Ann Arbor stage 3 or 4, albumin level <3.2 mg/L, number of extranodal sites >1, and involvement of retroperitoneal lymph node. We developed a new prognostic model consisting of these four factors. The 5-year probability of CNS relapse was significantly higher in patients with at least three of these four factors than in those with two or fewer factors (26.4 vs. 3.0 %, P < 0.001). Using this model, we evaluated the incidence and the risk factors of CNS relapse in DLBCL patients. The new risk model consisting of the four factors demonstrated good risk stratification for CNS relapse, and could help to identify high-risk patients for whom CNS prophylaxis is warranted.

Interstitial lung changes and persistent COVID-19 in a patient with follicular lymphoma: A case report.

We herein report a case of interstitial lung changes in a patient with prolonged coronavirus disease 2019 (COVID-19) with follicular lymphoma receiving rituximab and bendamustine who recovered after treatment with a combination therapy consisting of corticosteroids and immunosuppressive agents. There is currently no treatment strategy for prolonged pneumonitis following COVID-19, which can be life-threatening for immunocompromised patients. Thus, further investigation is warranted.

Early failure is still a poor prognostic factor in patients with relapsed or refractory large B-cell lymphoma in the era of CAR T-cell therapy.

Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.

Hemoglobin-platelet index as a prognostic factor in patients with peripheral T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with a poor prognosis. The International Prognostic Index (IPI) and the Prognostic Index for PTCL-unspecified (PIT) is used to predict the prognosis of PTCL. The hemoglobin-platelet index (HPI), based on anemia and thrombocytopenia status, is associated with the prognosis of diffuse large B-cell lymphoma. However, its significance in terms of predicting the prognosis of PTCL has not been fully investigated. We herein retrospectively analyzed 100 patients with newly diagnosed PTCL in our department. At a median follow-up of 3.2 years, the median progression-free survival (PFS) and overall survival (OS) was 0.72 (95% confidence interval [CI]: 0.56-1.2) years and 2.0 (95% CI: 1.5-4.7) years, respectively. Multivariate analysis revealed that elevated lactic dehydrogenase (LDH) and hypoalbuminemia were independent adverse variables for PFS. The HPI showed significant predictive value for both PFS and OS. As a new prognostic model comprising the HPI, LDH, and albumin, the LA-HPI allowed the stratification of patients into four distinct risk subgroups: low risk (zero risk factors), low-intermediate risk (one risk factors), high-intermediate risk (two or three risk factors), or high risk (four risk factors). The PFS and OS differed significantly among the patients by the LA-HPI score. The LA-HPI demonstrated better predictive performance compared to the IPI, PIT, and HPI. Our data demonstrated the prognostic utility of the HPI in patients with PTCL. The LA-HPI, incorporating four readily obtainable parameters, exhibited superior performance compared to traditional indices.

Clinical outcomes in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: A retrospective study.

OBJECTIVE: The prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Although patients who fail first-line salvage chemotherapy are candidates for second-line salvage chemotherapy, the optimal treatment strategy for these patients has not yet been established. METHODS: The present, single-center, retrospective study included transplant-eligible patients with R/R DLBCL who received second-line salvage chemotherapy with curative intent. RESULTS: Seventy-six patients with R/R DLBCL received second-line salvage chemotherapy. Eighteen (23.7%) patients were responders to the first-line salvage chemotherapy. The overall response rate was 39.5%, and overall survival (OS) was significantly longer in patients who responded to second-line salvage chemotherapy than those who did not. Forty-one patients who proceeded to potentially curative treatment (autologous hematopoietic stem cell transplantation [ASCT], chimeric antigen receptor [CAR] T-cell therapy, or allogeneic hematopoietic stem cell transplantation) had a better prognosis than those who did not. Among the 46 patients who failed to respond to the second-line salvage regimen, only 18 (39.1%) could proceed to the curative treatments. However, among the 30 patients who responded to the second-line salvage regimen, 23 (76.7%) received one of the potentially curative treatments. Among 34 patients who received CAR T-cell therapy, OS was significantly longer in those who responded to salvage chemotherapy immediately prior to CAR T-cell therapy than in those who did not respond. In contrast, the number of prior lines of chemotherapy was not identified as a statistically significant prognostic factor of survival. No significant difference was detected in OS between patients receiving ASCT and those receiving CAR T-cell therapy after the response to second-line salvage chemotherapy. DISCUSSION: In this study, we demonstrated that chemosensitivity remained a crucial factor in predicting survival outcomes following CAR T-cell therapy irrespective of the administration timing, and that both ASCT and CAR T-cell therapy were acceptable after the response to second-line salvage chemotherapy.