Peripheral Blood Lymphocyte-to-Monocyte Ratio at Relapse Predicts Outcome for Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma in the Rituximab Era

BackgroundPatients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis, even in the rituximab era. Several studies have reported the clinical importance of the peripheral blood lymphocyte-to-monocyte ratio (LMR) in various malignancies, including lymphoma. However, the prognostic value of the LMR in relapsed/refractory DLBCL has not been well evaluated. The purpose of the present study was to investigate whether the LMR at relapse can predict clinical outcomes for relapsed/refractory DLBCL patients treated with rituximab.Patients and MethodsWe analyzed data on 74 patients with relapsed/refractory DLBCL, who were initially treated with R-CHOP (rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone) or an R–CHOP-like regimen.ResultsThere was a significant association between a low LMR (≤ 2.6) and shorter overall survival (OS; P < .001) and progression-free survival (PFS; P < .001) compared with the high LMR group (> 2.6). Multivariate analysis showed that LMR was an independent prognostic factor for OS (P < .001) and PFS (P < .001), as was the international prognostic index (IPI) at relapse for OS. In addition, the LMR had an incremental value for OS and PFS compared with the IPI at relapse.ConclusionThe LMR predicts OS and PFS outcomes in relapsed/refractory DLBCL patients treated with rituximab, and might facilitate better stratification among patients in low- and intermediate-risk IPI groups.     

Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin's lymphoma

BackgroundThe purpose of this study was to assess prognostic factors and outcome of patients with relapsed/refractory Hodgkin's lymphoma (HL) who received high-dose chemotherapy and autologous stem-cell transplant (ASCT).Patients and methodsData on 195 patients who received ASCT between 1985 and June 2005 were reviewed. Median time from first treatment to ASCT was 2.6 years (0.4–27.3). Demography at ASCT was 61% stage IV, median age 31 years (18–69), median prior treatment (tx) regimens 3 (2–7), median Hasenclever index 3 (0–6); 150 patients had responding disease [54 complete remission (CR), 96 partial remission (PR)], and 45 patients had untested relapse/refractory disease.ResultsPost-ASCT, 61% (119/195) patients attained CR with an overall response (CR + PR) of 85%. Twelve patients had nonrelapse mortality. Of 119 patients attaining CR, 27 relapsed: 3 after attaining CR for >5 years and 1 after attaining CR for >10 years. Median overall survival (OS)/progression-free survival (PFS) from ASCT was 9 years/2.9 years. Five-year OS/PFS was 55% of 44% and 10-year OS/PFS was 49.4% of 37% for whole group. Twenty (10%) patients developed second cancer (seven secondary acute myeloid leukaemia (AML)/myelodysplastic syndrome (MDS)). Probability of developing second cancer at 10 years was 14.7% (95% confidence interval 8.9% to 23.8%) and 24.8% at 19 years.ConclusionThese data provide the longest follow-up reported for patients receiving ASCT for relapsed/refractory HL. In addition to previously described prognostic factors, our data show that Hasenclever index <3 influences outcome favorably and attaining CR at ASCT leads to a better outcome.     

Clinical characteristics and outcomes of relapsed follicular lymphoma after autologous stem cell transplantation in the rituximab era

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a therapeutic option for patients with relapsed follicular lymphoma (FL). The clinical characteristics and outcomes of FL relapse after ASCT in the rituximab era have not yet been fully elucidated. We retrospectively reviewed 414 FL patients treated with ASCT between 2000 and 2014 in four hematology departments. All patients received rituximab as a first-line treatment. We specifically analyzed the clinical characteristics, treatment strategies at relapse, and outcomes of 95 patients (23%) who relapsed after ASCT. The patients (median age, 57 y) received a median of two lines of therapy (range, 2-6) prior to ASCT, with 92% in complete response (CR) or partial response (PR) before ASCT. Histological transformation at relapse after ASCT was observed in 20% of the patients. Treatment at relapse after ASCT consisted of chemotherapy with or without rituximab (n = 45/90, 50%), targeted agents (18%), rituximab monotherapy (14%), or consolidation allogeneic transplantation after induction chemotherapy (12%) and radiotherapy (6%). After relapse, the median progression-free survival (PFS) and overall survival (OS) were 1 year (95% CI, 0.541-1.579) and 5.5 years (95% CI, 1.910-9.099), respectively. In the multivariate analysis, histological transformation (HT) was associated with OS (P = .044; HR 2.439; 95% CI, 1.025-5.806), and a high FLIPI score at relapse was associated with PFS (P = .028; HR 2.469; 95% CI, 1.104-5.521). This retrospective study showed that the period of PFS of patients who relapsed after ASCT is short. A biopsy should be performed for these patients to document the HT. Our results indicate that new treatment strategies will need to be developed for these patients.     

Effect of addition of rituximab to salvage chemotherapy on outcome of patients with diffuse large B-cell lymphoma relapsing after an autologous stem-cell transplantation

BackgroundWe have investigated if rituximab-based salvage regimens improve response rates and survival of patients with diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous stem-cell transplantation (ASCT).Patients and methodsWe have retrospectively analyzed 82 patients with DLBCL who received salvage therapy for relapse or progression after ASCT. Patients were divided into two groups, according to whether rituximab-based salvage regimens were given (n = 42, ‘R-’ group) or not (n = 40, ‘R+’ group) after ASCT.ResultsPatients in the R+ group had better complete remission (CR) (55% versus 21.4%, P = 0.006) and overall response (OR) (75% versus 40.4%, P = 0.001) rates, and better 3-year event-free survival (EFS) (37% versus 9%, P = 0.002) and overall survival (OS) (50% versus 20%, P = 0.005) than patients in the R- group. Patients retreated with rituximab had better CR (42.9% versus 21.4%, P = 0.032) and OR (66.7% versus 40.4%, P = 0.019) rates, and better OS (36.2% versus 20% at 3 years, P = 0.05) and EFS (36.2% versus 9% at 3 years, P = 0.05) than patients who received chemotherapy alone at relapse after ASCT.ConclusionsThe addition of rituximab to salvage chemotherapy improves response rates and EFS in patients with relapsed DLBCL after ASCT. These patients may benefit from rituximab retreatment, although larger prospective studies are needed to confirm these results.     

Identification of prognostic factors predicting outcome in Hodgkin's lymphoma patients relapsing after autologous stem cell transplantation

BackgroundHigh-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT.MethodsFive hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed.ResultsTreatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure.Conclusion(s)Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.     

Disease characteristics of diffuse large B-cell lymphoma predicting relapse and survival after autologous stem cell transplantation: A single institution experience

While various tools such as the International Prognostic Index (IPI) and its derivatives exist for risk-stratification of diffuse large B-cell lymphoma (DLBCL) at diagnosis, patient and disease characteristics capable of predicting outcome after high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) are not clearly defined. We retrospectively analyzed medical records of 111 DLBCL patients (78 relapsed and 33 refractory) who underwent HDC/ASCT at our institution from 2010-2015. After a median follow-up time of 4.6 years (interquartile range [IQR] 2.2-8.1), the likelihood of 5-year progression-free survival (PFS) was 62.2% (95% CI, 53.4%-72.4%) and the likelihood of 5-year overall survival (OS) was 68.9% (95% CI, 60.7%-78.2%). More than three chemotherapy regimens prior to ASCT was the only variable associated with lower likelihood of PFS (P = .004) and OS (P = 0.026). Male gender and high IPI score at time of ASCT were also associated with lower likelihood of PFS (P = .043; P = .013). NCCN IPI and age-adjusted IPI at time of ASCT were not predictive of outcome following ASCT. Patients with refractory and relapsed disease had similar outcomes post-ASCT (P = .207 for PFS, P = .073 for OS).     

Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial

BackgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma and despite recent chemotherapeutic advances up to half of all patients relapse. Here we report the results from a phase 2, single-arm, single-center trial evaluating the safety and efficacy of lenalidomide plus rituximab in elderly patients with relapsed or refractory DLBCL.Patients and MethodsBetween March and June 2009, elderly patients (65 years of age or older) with relapsed/refractory DLBCL who had been heavily pretreated were recruited. Oral lenalidomide (20 mg/d for 21 days of each 28-day cycle) was initiated for four cycles and rituximab (375 mg/m²) was administered on day 1 and day 21 of each 28-day cycle for four cycles. After this induction phase, patients achieving a complete response (CR), partial response (PR), or stable disease (SD) were given lenalidomide maintenance therapy at the same schedule for another 8 months.ResultsA total of 23 patients with a median of three prior treatments (range, 2 to 8) were included. The overall response rate (CR + PR) at the end of the induction phase was 35% (n = 8). Ten patients (7 CR, 1 PR, and 2 SD patients) were eligible for lenalidomide maintenance and 8 of these patients achieved a CR. Adverse events were manageable and the most common included neutropenia and thrombocytopenia.ConclusionOral lenalidomide in combination with rituximab is active in elderly patients with relapsed/refractory DLBCL with a high percentage of patients achieving a continuous CR after lenalidomide maintenance.     

Outcomes Related to FDG-PET-CT Response in Patients With Hodgkin Lymphoma Treated With Brentuximab-Vedotin at Relapse or Consolidation

BackgroundBrentuximab-vedotin (BV) monotherapy has shown high efficacy in heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma (HL) after high-dose chemotherapy or autologous stem cell transplantation (ASCT). We retrospectively analyzed the outcomes of treatment with BV of HL patients and examined the predictive ability of PET-CT for response in this setting.Patients and methodsRecords of 49 HL patients (median age, 39 years, 55% male) treated with BV for relapse (71.4%) or consolidation (28.6%) post-ASCT were analyzed. Patients who did not reach complete response (CR) on PET/CT after 4 cycles (non-responders) discontinued BV and received the next treatment line. Overall survival (OS) and progression-free survival (PFS) were compared between responders and non-responders.ResultsAfter a median follow-up of 19.1 months, all consolidation patients were alive and none progressed. Median OS in 23 relapsed patients that did not achieve CR after 4 cycles and continued to the next treatment was 55.0 months, while all those in CR (n = 24) were alive (P = .0120). No statistically significant differences in OS were observed between responders and non-responders with relapsed HL (P = .1072). Median PFS evaluated after 4 BV cycles was significantly longer in responders compared to non-responders (47.9 vs. 1.5 months, P < .0001). Neuropathy and neutropenia were the main toxicities observed.ConclusionsHL patients treated with BV for relapse or consolidation who achieved CR by PET-CT after 4 cycles showed improved PFS and OS compared to non-responders. Non-responders treated for relapsed HL who proceeded to the next treatment line demonstrated comparable OS to responders.     

CD5-positive diffuse large B-cell lymphoma: a retrospective study in 337 patients treated by chemotherapy with or without rituximab

BackgroundCD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) shows poor prognosis and frequent central nervous system (CNS) relapses under anthracycline-containing chemotherapy. The aim of this study was to determine the prognosis and CNS relapse incidence of CD5+ DLBCL in the rituximab era.Patients and methodsWe analyzed 337 patients with CD5+ DLBCL who received chemotherapy with (R-chemotherapy group; n = 184) or without (chemotherapy group; n = 153) rituximab.ResultsNo significant difference was found in clinical background comparisons between the two groups. In the R-chemotherapy group, 60% of the patients were older than 65 years at diagnosis. Both the complete response rate and overall survival (OS) were significantly better in the R-chemotherapy group (P = 0.0003 and P = 0.002, respectively). Multivariate analysis confirmed that chemotherapy without rituximab was associated with unfavorable OS. However, the probability of CNS relapse did not differ between the two groups (P = 0.89). The CNS relapse was strongly associated with short OS (P < 0.0001). In the R-chemotherapy group, 83% of patients who experienced CNS relapse had parenchymal disease.ConclusionsOur results indicate that rituximab improves the OS of patients with CD5+ DLBCL but does not decrease the CNS relapse rate. More effective treatments with CNS prophylaxis are needed for CD5+ DLBCL patients.     

Relapse in stage I(E) diffuse large B‐cell lymphoma

Despite a general favourable outcome in limited stage diffuse large B‐cell lymphoma (DLBCL), relapses occur in about 10 to 20% of patients. Prognostic models only partially identify patients at risk for relapse. Moreover, it is not known whether the outcome after such a relapse is similar to the outcome after relapse in advanced stages. From January 2004 through December 2012, all newly diagnosed patients with stage I(E) DLBCL were retrospectively analysed from 2 clinical databases to investigate the relapse pattern and outcome in relation to initial treatment and clinical characteristics. In 126 patients (median age 64 years), histologically confirmed stage I(E) DLBCL was diagnosed. With a median follow‐up of 53 months (range 5‐132 months), 1 progressive disease and 18 relapses occurred. The 5‐year time to tumour progression and disease‐specific survival were 85% (95% CI 79‐91%) and 92% (95% CI 87%‐97%), respectively. We observed no significant difference in relapse localization, time to tumour progression, and disease‐specific survival between patients treated with abbreviated R‐CHOP plus involved field radiotherapy or with 6 to 8 cycles of R‐CHOP. Analysis of relapses showed relapse >5 years after initial treatment (late relapse) in 5 of 19 patients (26%). Six of 19 patients (32%) had central nervous system relapse. Three of 11 relapsed cases available for analysis (28%) showed an MYC translocation, suggesting an overrepresentation in the relapse group. Outcome of patients with a relapse was poor with a median survival after relapse of 8 months. Only 1 patient (5%) underwent successful autologous stem cell transplantation. To improve outcome in these patients, early identification of new biological factors such as a MYC translocation or a high risk for CNS dissemination might be helpful. Moreover, treatment of any relapse after stage I disease should be taken seriously. Salvage treatment should be similar to relapses after advanced DLBCL.     

Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies

IntroductionMelphalan flufenamide (melflufen), a first-in-class alkylating peptide-drug conjugate, plus dexamethasone demonstrated superior progression-free survival (PFS) but directionally different overall survival (OS) favoring pomalidomide (hazard ratio [HR], 1.10) in OCEAN.MethodsThese analyses further investigated prognostic subgroups impacting survival in updated data from the randomized, phase 3 OCEAN study (NCT03151811; date: February 3, 2022) and the phase 2 HORIZON study (NCT02963493; date: February 2, 2022).ResultsIn OCEAN, subgroups prognostic for OS were age (P = .011; <65 years favored pomalidomide) and no previous autologous stem cell transplant (ASCT) or progression >36 months after ASCT (P = .001; favored melflufen). Overall, 245 of 495 (49%) patients randomized had received a previous ASCT, of which 202 (82%) had progressed within 36 months following their ASCT. When excluding patients who had progressed <36 months post-ASCT (melflufen group, n = 145; pomalidomide group, n = 148), median OS was 23.6 months with melflufen and 19.8 months with pomalidomide (HR, 0.83 [95% CI, 0.62-1.12]; P = .22). Among patients with triple-class refractory disease in HORIZON, patients who had progressed <36 months post-ASCT (n = 58) had a lower response rate and shorter duration of response and PFS than the remaining patients (n = 52). Safety was consistent with previous reports.ConclusionThese analyses demonstrate a consistent benefit for melflufen and dexamethasone in patients with relapsed/refractory multiple myeloma who have not received an ASCT or progressed >36 months after receiving an ASCT (ClinicalTrials.gov identifier: NCT03151811).     

Patterns of Relapse After Salvage Autologous Stem Cell Transplant for Hodgkin's Lymphoma: Should Sites of Relapse Relative to Initially Involved Sites Be Used to Guide Indications for Peri-Transplant Radiation Therapy

PurposeWe aimed to assess patterns of relapse in patients undergoing salvage autologous stem cell transplant (ASCT) for relapsed Hodgkin lymphoma in the modern era with the hypothesis that patients who suffer a relapse at initially involved sites are at increased risks of relapse post-ASCT that may help guide the application of peri-transplant radiation therapy.Methods and MaterialsA retrospective review was conducted of 38 patients undergoing ASCT between 2002 and 2017 for relapsed or refractory Hodgkin lymphoma. The site of relapse at the time of ASCT and subsequent relapses were compared with sites of the initial involvement at the time of diagnosis using follow-up imaging (most commonly positron emission computed tomography). Relapse and overall survival rates were calculated from the date of ASCT using the Kaplan-Meier method with a multivariate analysis, completed using a Cox multivariate analysis.ResultsThe median follow-up time was 38 months (interquartile range, 18-66 months). Twenty-two patients (58%) suffered a relapse after ASCT at a median time to relapse of 9.1 months (interquartile range, 2.9-12.3 months) with a 5-year risk of relapse of 58% (95% confidence interval [CI], 41%-75%). On univariate analysis, relapse at an initially involved site was significant for higher rates of relapse at 71% at 5-years (95% CI, 52%-90%) compared with relapse at initially uninvolved sites at 30% (95% CI, 2%-58%; P = .05). The relapse rate was also significantly higher in patients age <30 years at the time of diagnosis at 80% (95% CI, 59%-100%) compared with 40% (95% CI, 18%-62%) at 5 years in patients aged >30 years (P < .01). On multivariate analysis, relapse at initially involved sites was significant for higher rates of relapse (hazard ratio: 8.3; 95% CI, 1.2-57.4; P = .03).ConclusionsRelapses at initially involved sites may potentially increase the risk of relapse after ASCT. Additional studies are needed to clarify whether this should be used as an additional factor to guide recommendations for peri-transplant radiation therapy.     

Rituximab,Dexamethasone, Cytarabine,and Oxaliplatin (R-DHAX) Is an Effective and Safe Salvage Regimen in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

BackgroundSalvage therapy for patients with refractory/relapsed B-cell non-Hodgkin lymphoma (NHL) is based on polychemotherapy, followed by high-dose therapy and autologous stem cell transplantation in eligible patients (HDT/ASCT). R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone.Patients and MethodsWe substituted cisplatin with oxaliplatin to avoid nephrotoxicity and retrospectively analyzed a large series of 91 patients with refractory/relapsed B-cell NHL to evaluate toxicities, response rates (RRs), and survival. Median age at R-DHAX (rituximab/dexamethasone/cytarabine/oxaliplatin) treatment was 60 years (range, 28-82 years). Renal insufficiency was present in 18 patients. The most frequent histologic subtypes were diffuse large B-cell lymphoma (n = 42) and follicular lymphoma (n = 30). Seventeen patients (19%) were naive to rituximab at time of R-DHAX.ResultsGrade III/IV toxicities were mainly hematologic, including anemia (n = 9), neutropenia (n = 44), and thrombocytopenia (n = 47). Grade I/II neurologic toxicities, sensitive or motor, were observed, and these were mainly transient except for 3 cases of motor neuropathy associated with previous exposure to vincristine. Neither renal toxicities nor degradation of previous renal insufficiency were observed. The overall RR was 75%, with a complete RR of 57%, with no statistical difference between patients previously treated with rituximab versus without rituximab. At a median follow-up of 23 months, 2-year probability rates of overall survival and progression-free survival were 75% and 43%, respectively, with a significant difference between patients treated with HDT/ASCT and patients not eligible for HDT/ASCT.ConclusionR-DHAX is an efficient regimen in patients with relapsed/refractory B-cell NHL even in elderly patients if hematologic toxicities are closely managed.     

Outcome of patients with transformed indolent non-Hodgkin lymphoma referred for autologous stem-cell transplantation

BackgroundThe proportion of potentially eligible patients with transformed indolent non-Hodgkin lymphoma who undergo autologous stem-cell transplantation (ASCT) is unknown. There are limited data describing their outcome in the rituximab era.Patients and methodsWe reviewed 105 consecutive patients with biopsy-proven transformation referred to Princess Margaret Hospital for consideration of ASCT during 1996–2009. Patients received anthracycline or platinum-based chemotherapy with or without rituximab. Responders proceeded to stem-cell mobilization and ASCT.ResultsThe median age at transformation was 54 (range 30–65) years. Patients received a median of two chemotherapy regimens for transformation, including rituximab in 39%. Fifty patients (48%) proceeded with ASCT and 55 (52%) did not, mainly due to progressive disease (n = 42). Three-year overall (OS) and progression-free survival (PFS) post-ASCT were 54% and 42%, respectively. Patients receiving rituximab with chemotherapy before transplant had a 3-year post-ASCT OS of 71% versus 47% in those who received chemotherapy alone (P = 0.046). Patients transplanted after 2004 had a 3-year post-ASCT OS of 69% versus 39% in those receiving ASCT earlier (P = 0.009).ConclusionsAbout half of transplant-eligible patients with transformation are able to undergo ASCT. Outcomes following ASCT appear to have improved over recent years, although the role of rituximab in this patient population requires further evaluation.     

Early Relapse After Autologous Transplant Is Associated With Very Poor Survival and Identifies an Ultra-High-Risk Group of Patients With Myeloma

IntroductionPatients relapsing early after autologous stem cell transplantation (ASCT) are a particular therapeutic challenge.MethodsThis was a retrospective, single center study that included 297 consecutive patients that received first-line ASCTResultsWe identified 43 (14.5%) patients that relapsed within <12 months. At diagnosis, these patients had more often elevated lactate dehydrogenase, lower estimated glomerular filtration rate, hypercalcemia, and high-risk cytogenetics; the International Staging System stage distribution was similar. Consolidation and maintenance were associated with lower rates of early relapses. Progression-free survival to second-line therapy was 5 months versus 19 months for those with an early versus late relapse (P < .001), the median PFS to second-line therapy was 15.5 months versus >5 years (P < .001) and the median post-ASCT survival was 18 months versus >6 years. The survival after an early relapse has not improved significantly over time. In multivariate analysis, early relapse (hazard ratio, 14; P < .001) was the most important prognostic factor for poor survival after ASCT.ConclusionPatients relapsing <12 months after ASCT comprise an ultra-high-risk group, with poor outcomes even with the application of the more recent combinations, that urgently needs more effective therapies.     

High-dose chemotherapy followed by autologous stem cell transplantation for relapsed or refractory Hodgkin lymphoma: prognostic features and outcomes

Between January 1990 and April 2001, 115 patients received high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) for relapsed or refractory Hodgkin lymphoma (HL). With a median follow-up of 58 months (range, 1 - 175 months), 5-year progression-free survival (PFS) and overall survival (OS) were 46% and 58%, respectively. Twelve patients with primary refractory disease had a 5-year PFS of 41% and OS of 58%, not significantly different from those of the remaining cohort. Early and overall regimen related mortality were 7% and 16%, respectively. Male gender (P = 0.04) and a time to relapse (TTR) < 12 months (P = 0.03) were associated with decreased OS by univariate analysis. In multivariate analysis, TTR < 12 months remained statistically significant (P = 0.04). We have confirmed that HDT and ASCT result in long-term survival for a proportion of patients with relapsed or refractory HL. All patients, including those with primary refractory disease, benefited from HDT and ASCT.     

Post Salvage Therapy Autologous Transplant for Relapsed Myeloma,Ongoing Relevance within Modern Treatment Paradigms?

BackgroundSalvage transplant has been historically considered effective therapy for myeloma patients relapsing after first transplant, if they achieved adequate remission duration. However, the efficacy of novel agent combinations has called this paradigm into question.Materials and MethodsWe performed a retrospective analysis in a homogeneously treated cohort of 106 patients undergoing ASCT2 at our institution, all of whom received novel agent-based chemotherapy (immunomodulatory agent [IMiD] and/or proteasome inhibitor [PI]) for both induction and relapse. As an exploratory objective we assessed whether predictive thresholds of progression free survival post first transplant (ASCT1) for benefit post ASCT2 vary with use of IMiD maintenance post ASCT1.ResultsThe overall response rate (ORR) was 98% post-ASCT2 and treatment-related mortality (TRM) was low at 1.8%. With a median follow-up of 26 months (range 0.5-85) from ASCT2, median overall survival (OS) is estimated at 80 months (95% CI: ≥ 49-months) and median progression-free survival after ASCT2 (PFS2) at 24 months (95% CI 19-39). PFS post first transplant (PFS1) at >/= 50 months was associated with improved OS. Predictors of PFS2 included PFS1 ≤42 months and progression on IMiD-based maintenance post- ASCT1.ConclusionASCT2 continues to offer acceptable outcomes for most patients treated within modern day treatment paradigms, with longer PFS after ASCT1 and IMiD non-refractory disease being associated with improved outcomes     

Patterns of Utilization and Outcomes of Autologous Stem Cell Transplantation and Chimeric Antigen Receptor T-Cell Therapy in Relapsed or Refractory Diffuse Large B-cell Lymphomas with MYC and BCL2 and/or BCL6 Rearrangements

BackgroundPatients with Diffuse Large Bcell Lymphoma (DLBCL) with MYC and BCL2 and/or BCL6 gene rearrangements [double-hit lymphoma/triple-hit lymphoma (DHL/THL)] have poor prognosis in the relapsed/refractory setting.MethodsWe utilized a real-world deidentified database of DLBCL patients and report patterns of therapy utilization in relapsed/refractory DLBCL. We used log-rank test to compare real-world overall survival (rwOS) among DHL and non-DHL subgroups for CAR Tcell therapy or ASCT respectively, stratified for prior lines of therapy.ResultsOf all 7,877 patients with DLBCL, 367 patients had DHL while 6113 had non-DHL. Second line chemotherapy was administered to 147 DHL patients and 1517 non-DHL. 1393 were excluded, including 934 with unknown DHL/THL status. Approximately 47% received salvage intent chemotherapy in the DHL subgroup, of which 19% patients eventually received ASCT, while 34% received salvage intent chemotherapy in the non-DHL/THL group with 32% receiving ASCT. DHL/THL status negatively influenced median rwOS for patients who underwent ASCT in the second-line while it was associated with numerically inferior but without statistically significant rwOS among patients that underwent CAR Tcell therapy on multivariable analysis.ConclusionrwOS of relapsed DHL/THL is inferior to non-DHL/THL. Fewer patients with DHL/THL were able to proceed with ASCT after salvage chemotherapy compared to non-DHL/THL. ASCT as second-line therapy for relapsed DHL/THL had worse rwOS than for non-DHL/THL, consistent with the natural history of DHL/THL. This difference was not seen for CAR Tcell therapy, which combined with promising results from clinical trials, suggests a greater role for CAR T-cell therapy in relapsed/refractory DHL.     

Retrospective Analysis of the Efficacy and Tolerability of Gemcitabine-Based Chemotherapy in Relapsed/Refractory Lymphoma Patients Not Eligible for Stem Cell Transplant

IntroductionGemcitabine-based regimens are effective salvage therapy for RR lymphoma patients eligible for ASCT, but there is limited data in transplant-ineligible (TIE) patients. Here, we present a retrospective analysis on the outcome of TIE adult patients with RR lymphoma treated with gemcitabine, cisplatin or carboplatin and dexamethasone (GDP/GDCarboP) +/- rituximab regimen in our center.PatientsWe identified 33 patients: 54.5% diffuse large Bcell lymphoma (DLBCL), 6.1% double/triple hit lymphoma, 15% follicular lymphoma, 18% T-cell lymphoma, and 6% classical Hodgkin lymphoma. Majority of the patients had advanced-stage disease and raised LDH at relapse. The cohort's median age was 71 years. The median number of prior lines of treatment was 2, and 60.6% were refractory to their last line of treatment.ResultsThe overall response rate was 33% (complete response 15%) for the entire cohort and 62.5% for DLBCL patients not refractory to prior line of treatment. At median follow-up of 25 months, the median duration of response and overall survival in the responders were not reached. Conversely, the median overall survival for the non-responders was dismal at 5 months. Fifty-five percent required treatment alteration (dose attenuation or omission and treatment delay for >1 week) due to adverse events, 73% needed transfusion, and 70% had at least 1 hospital admission during treatment.ConclusionOur real-world data showed that GDP/GDCarboP provides meaningful efficacy and durability, especially among the responders. However, dose modification and inpatient support are frequently needed, indicating the need for good supportive care and close follow-up in this frailer population.     

Bendamustine plus rituximab for relapsed or refractory diffuse large B cell lymphoma: a retrospective analysis

For patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who are not eligible for intensive chemotherapy because of comorbidities, advanced age, or relapse after heavy salvage regimens, treatment options are very limited and prognosis is poor. We retrospectively analyzed 29 patients with relapsed/refractory DLBCL treated with combination bendamustine plus rituximab (BR) between July 2010 and January 2014 to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR) and treatment safety. Twenty-eight patients were available for this analysis. ORR was 50% (14 patients), with 39.3% CR (11 patients), and 10.7% PR (3 patients). SD was reported in 2 patients (7.2%) and PD in 12 patients (42.8%). At the median follow up of 8 months (range 1–37.4 months), the median PFS was 8 months for all patients (95% CI 5.5–26.6). The median DOR was 24.7 months (95% CI 3.2–24.7). Grade 3/4 toxicity observed included hematologic events: lymphopenia (42.8%), neutropenia (32.1%), anemia (17.2%), and thrombocytopenia (14.2%). BR can be considered to have a role in the treatment of patients with relapsed/refractory DLBCL with limited therapeutic options, in that it can induce long-term remission in some patients with an acceptable toxicity profile.