Modified R-BAC plus BTK inhibitor regimen in newly diagnosed young patients with mantle cell lymphoma: a real-world retrospective study.

To explore the optimal treatment for young patients with untreated mantle cell lymphoma (MCL), we compared the efficacy and safety of R-CHOP/R-DHAP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone/rituximab, dexamethasone, cytarabine and cisplatin) and R-BAP (rituximab, bendamustine, cytarabine, and prednisone) plus BTK (Bruton's tyrosine kinase) inhibitors in newly diagnosed patients. Eighty-three young patients (≤ 65 years old) with newly diagnosed MCL admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2014, to June 1, 2023, using R-CHOP/R-DHAP or R-BAP plus BTK inhibitor were assessed in this study. The median age at presentation was 60 (42-65) years in 83 patients, including 64 males and 19 females; 59 were treated with R-CHOP/R-DHAP regimen chemotherapy, and 24 were treated with R-BAP in combination with the BTK inhibitor regimen. The median follow-up was 17 months (2-86 months) in 83 patients, and the median PFS (progression-free survival) time was not reached. The CRR (complete response rate) of the R-BAP group was higher than that of the R-CHOP/R-DHAP group (87.5% vs. 54.2%, P = 0.005). The ORR (overall response rate) was not significantly different between the two groups (ORR: 91.7% vs. 84.7%, P = 0.497). The PFS (progression-free survival) of the R-BAP group was longer than that of the R-CHOP/R-DHAP group (P = 0.013), whereas OS was not significantly different between the two groups (P = 0.499). The most common adverse effect in both groups was hematotoxicity, with a higher incidence of grade 3-4 lymphopenia and grade 3-4 thrombocytopenia in the R-BAP group than in the R-CHOP/R-DHAP group (P = 0.015 and P = 0.039). Male sex (HR = 4.257, P = 0.013), LDH (lactate dehydrogenase) ≥ 245 U/L (HR = 3.221, P = 0.012), pleomorphic-blastoid (HR = 2.802, P = 0.043) and R-CHOP/R-DHAP regimen (HR = 7.704, P = 0.047) were independent risk factors for PFS. Ki67 ≥ 30% (HR = 8.539, P = 0.005) was an independent risk factor for OS. First-line treatment with R-BAP in combination with BTK inhibitor improved CRR and prolonged PFS in young patients with mantle cell lymphoma and adverse events were tolerable.

First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia.

BACKGROUND: Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. METHODS: In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, <10-4 [i.e., <1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival. RESULTS: A total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax-rituximab, 229 to venetoclax-obinutuzumab, and 231 to venetoclax-obinutuzumab-ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax-obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44.4 to 59.5; P<0.001 for both comparisons), but it was not significantly higher in the venetoclax-rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P = 0.32). Three-year progression-free survival was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P<0.001). Progression-free survival at 3 years was also higher with venetoclax-obinutuzumab (87.7%; hazard ratio for disease progression or death, 0.42; 97.5% CI, 0.26 to 0.68; P<0.001), but not with venetoclax-rituximab (80.8%; hazard ratio, 0.79; 97.5% CI, 0.53 to 1.18; P = 0.18). Grade 3 and grade 4 infections were more common with chemoimmunotherapy (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%). CONCLUSIONS: Venetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL. (Funded by AbbVie and others; GAIA-CLL13 ClinicalTrials.gov number, NCT02950051; EudraCT number, 2015-004936-36.).

A phase I/II study of 10-min dosing of bendamustine hydrochloride (rapid infusion formulation) in patients with previously untreated indolent B-cell non-Hodgkin lymphoma, mantle cell lymphoma, or relapsed/refractory diffuse large B-cell lymphoma in Japan.

PURPOSE: This phase I/II clinical study was conducted to examine the safety, tolerability, pharmacokinetics, and efficacy of 10-min dosing of bendamustine in patients with previously untreated indolent B-cell non-Hodgkin lymphoma (iNHL) or mantle cell lymphoma (MCL) (Group 1) and patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) (Group 2). METHODS: Rituximab 375 mg/m2 was administered intravenously every 28 days to Group 1 patients on day 1 and every 21 days to Group 2 patients on day 1. Bendamustine 90 mg/m2/day was administered to the former on days 1 and 2; bendamustine 120 mg/m2/day was administered to the latter on days 2 and 3. Each regimen was delivered up to six cycles for both groups. The primary endpoints were safety and tolerability in Groups 1 and 2, respectively. RESULTS: Among 37 enrolled patients, safety was assessed in 36. In Group 1 (n = 30), 27 patients (90%) had follicular lymphoma. Adverse events (AEs) were observed in all 30 patients in Group 1. Dose-limiting toxicities were observed in two of six patients in Group 2. Common AEs included lymphocyte count decreased (86.7%, 100%). In Group 1, overall response and complete response rates were 93.1% (95% confidence interval [CI] 77.2-99.2%) and 75.9% (95% CI 56.5-89.7%), respectively. The Cmax and AUC of bendamustine tended to be higher in Group 2 than in Group 1. CONCLUSIONS: This study showed that bendamustine is safe, well-tolerated and effective for patients with previously untreated iNHL, MCL or rrDLBCL. Pharmacokinetic data were equivalent to those obtained outside of Japan. REGISTRATION NUMBERS: Registration NCT03900377; registered April 3, 2019.

Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma.

BACKGROUND: Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS: We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed. RESULTS: Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P = 0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group. CONCLUSIONS: Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs. (Funded by Janssen Research and Development and Pharmacyclics; SHINE ClinicalTrials.gov number, NCT01776840.).

Follicular Lymphoma: a Focus on Current and Emerging Therapies

Follicular lymphoma (FL) is the most common indolent lymphoma and is characterized by a relapsing and remitting course. In addition to significant biologic heterogeneity, the clinical trajectory for patients is variable, with some being observed for many years, and others having aggressive disease requiring multiple treatment courses. Unfortunately, FL remains incurable, and continues to cause early mortality. Improved understanding of the genetic and immune biology of FL has led to several FDA-approved therapies in the relapsed and refractory setting, including PI3K inhibitors; immunomodulatory agents; the EZH2 inhibitor, tazemetostat; and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel. This review outlines the current approach to the diagnosis and treatment of FL with a focus on emerging investigational therapies, including targeted protein inhibitors, antibody-drug conjugates, monoclonal antibodies, bispecific antibodies, and novel combination strategies.

Clinical Efficacy of Bendamustine Plus Rituximab (BR) for B-cell Relevant Indolent Non-Hodgkin's Lymphoma and Role of ß2-MG in Predicting the Efficacy of BR Regimen: A Real-World Retrospective Study in China.

BACKGROUND: Domestic bendamustine has been approved for appearing on the market in China in the past two years. The report on bendamustine plus rituximab (BR) in the treatment of Chinese B-cell-associated indolent non-Hodgkin's lymphoma (iNHL) has not yet been published. This study probed into clinical efficacy of the BR regimen for B-cell-associated iNHL in China as well as the value of ß2-microglobulin (ß2-MG) as a prognostic factor. METHODS: We retrospectively analyzed clinical data of 73 B-cell-associated iNHL patients who received BR treatment in The First Affiliated Hospital, College of Medicine, Zhejiang University from January 2020 to January 2021, including clinical characteristics, therapies, therapeutic efficacy, and prognosis-related factors. Thirty-three patients (45.2%) did not receive any other treatment before the BR regimen, and other patients received CHOP, R-CHOP, and other regimens in the past. The cutoff date for follow-up was May 2021. Clinical characteristics of patients were analyzed. The clinical efficacy of the BR regimen was evaluated. Differences of ß2-MG expression before and after treatment were analyzed between the CR+PR group and the SD+PD group. Main outcomes were progression-free survival (PFS) and overall survival (OS). A multivariate Cox regression model was taken to analyze prognostic factors relative to survival rate of patients, and adverse events (AEs) during treatment. RESULTS: The objective response rate (ORR) of B-cell-associated iNHL patients who received BR regimen as first-/multiline treatment was 79.5%, with complete response (CR) of 37.0%, partial response (PR) of 42.5%, median PFS of 12.1 months (95% confidence interval (CI): 10.9-13.2), and median OS of 15.5 months (95% CI: 14.8-16.1). Before treatment, there was no statistical significance in the ß2-MG level between the CR+PR group and the SD+PD group (p > 0.05). After treatment, the ß2-MG level in the CR group was noticeably lower than that in the SD+PD group (p < 0.05). The ß2-MG level in the CR+PR group decreased conspicuously after treatment (p < 0.05). The ß2-MG level in the SD+PD group after treatment was not notably different from that before treatment (p > 0.05). According to the median expression level of ß2-MG before treatment, patients were divided into two groups. The average PFS of the low expression group was 12.69 ± 0.77 months, which was longer than the high expression group (10.13 ± 0.74 months), but the difference between the groups was not statistically significant (p > 0.05). Multivariate Cox regression analysis showed that B-cell-associated iNHL subtype was the independent prognostic marker most likely to affect PFS of patients (p = 0.051). Incidence of any grade of AEs in all patients was 32.9% (24/73). CONCLUSION: B-cell-associated iNHL patients who received BR regimen had favorable clinical efficacy and were tolerable to AEs. Though the ß2-MG level in this study could not be used to predict clinical outcome, a lower level before treatment seemed to be implicated in better survival outcomes of patients. Our research also unraveled that B-cell-associated iNHL subtype may be a key factor to patient's prognosis. Overall, this study offers some important insights into clinical application of the BR regimen for Chinese B-cell-associated iNHL patients.

Pre-treatment health-related quality of life parameters have prognostic impact in patients >65 years with newly diagnosed mantle cell lymphoma: The Nordic Lymphoma Group MCL4 (LENA-BERIT) experience.

Mantle cell lymphoma (MCL) is a rare, often aggressive type of B-cell lymphoma with poor survival and no cure. Cancer and cancer treatment has a negative impact on health-related quality of life (HRQOL) both during active disease and in the long term, and improvement of HRQOL is a crucial objective of cancer therapy in older patients and no curative intent. Baseline HRQOL has in other lymphoma populations been shown to be predictive of outcome. Here, we explored HRQOL, and its association with survival, by the EORTC QLQ-C30 questionnaire, before, during and after chemotherapy in a patient cohort with MCL, treated within the NLG-MCL4 trial, designed to evaluate the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment. Fifty-one patients were enrolled, median age was 71 years (range 62-84), 37 were men (73%). Pre-treatment HRQOL was similar to scores from the reference population with healthy individuals. During treatment, HRQOL deteriorated, but reverted to the same level as the reference population after treatment. There was a correlation between physical function (p = 0.001) and role function (p = 0.006) at baseline and WHO performance status, but not with other clinical or genetic prognostic factors. None of the baseline factors were predictive for treatment related to HRQOL in this cohort. Pre-treatment physical (p = 0.011) and role function (p = 0.032) were independent factors associated with overall survival, and physical function (p = 0.002) was also associated with progression free survival. These findings may possibly be used to design support during treatment and improve rehabilitation. Further investigations are needed for assessment of long-term HRQOL.

Sequencing of Novel Therapies for Mantle Cell Lymphoma.

OPINION STATEMENT: There is no standard approach to sequencing novel therapies in mantle cell lymphoma (MCL). For initial treatment, intensive induction chemotherapy followed by autologous stem cell transplant and rituximab maintenance remains our preferred approach in young, fit patients. We consider bendamustine plus rituximab or lenalidomide plus rituximab in patients who are ineligible for intensive chemotherapy-based approaches. Bruton's tyrosine kinase inhibitors are our preferred class of agents to use in the second-line setting. When patients inevitably relapse on one of these agents, we proceed with chimeric antigen receptor T-cell (CAR T) therapy in eligible patients, often with the use of bridging therapy with corticosteroids, lenalidomide, or venetoclax. We treat patients who are ineligible for CAR T or clinic trial with venetoclax, lenalidomide, or proteosome inhibitor-based regimens, although efficacy is expected to be limited in this setting with a shortened duration of response to each subsequent line of therapy. Allogeneic stem cell transplant remains an option for carefully selected patients who progress after autologous stem cell transplant and CAR T. Clinical trials involving combinations of novel agents in early lines of therapy are ongoing, and new compounds with unique mechanisms of action are in development. The results of ongoing clinical trials with novel agents will further change the treatment landscape for patients with MCL in the coming years.

Novel Therapies for Follicular Lymphoma and Other Indolent Non-Hodgkin Lymphomas.

OPINION STATEMENT: When selecting therapy for patients with indolent non-Hodgkin lymphoma (iNHL) including follicular (FL), marginal zone (MZL), small lymphocytic (SLL), and lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM), there are several factors to consider. With a median age around 70 at diagnosis, many patients have accumulated comorbid conditions that may limit treatment options. Although incurable for most, iNHL is a chronic disease with a median overall survival measured in years to decades. This long natural history changes the risk-to-benefit balance with a lower acceptance of toxicity early in the treatment course compared to that of aggressive lymphomas. Despite a recent rapid increase in available therapies, overall progress in iNHL has been slow for several reasons. Initial trials grouped iNHLs together making it challenging to appreciate the differential activity among subtypes. We have not been able to develop prognostic models that maintain validity in the era of chemotherapy-free options. Predictive markers have been elusive and without identified molecular signatures, it is challenging to select and sequence therapy. With these clinical factors in mind, in addition to the heterogeneity among and within iNHLs, I do not have a standard treatment algorithm and feel each patient should have an individualized treatment approach. This review focuses on recent updates and controversies in the management of iNHL with a focus on FL and MZL.

How to Sequence Therapies in Waldenström Macroglobulinemia.

OPINION STATEMENT: There are multiple treatment options in patients with Waldenström macroglobulinemia, including chemotherapy, monoclonal antibodies, proteasome inhibitors, and covalent Bruton tyrosine kinase (BTK) inhibitors. The choice of therapy should take into account the patient's clinical presentation, comorbidities, and preferences. A thorough discussion should take place to outline the administration, safety, and efficacy of the regimens under consideration. The patient's genomic profile can provide insightful information for the treatment selection. In the frontline and relapsed settings, we favor ibrutinib monotherapy over chemoimmunotherapy or proteasome inhibitor-based regimens in patients with MYD88 and without CXCR4 mutations. For patients with MYD88 and CXCR4 mutations or without MYD88 or CXCR4 mutations, chemoimmunotherapy or proteasome inhibitor-based regimens are favored, but efficacy data with ibrutinib in combination with rituximab and with novel covalent BTK inhibitors are emerging. Autologous stem cell transplant should be considered in special cases in the relapsed setting. Participation in clinical trials is positively encouraged in WM patients in frontline and relapsed settings. Agents of interest include the BCL2 antagonist venetoclax, the CXCR4 inhibitor mavorixafor, and the non-covalent BTK inhibitors pirtobrutinib and ARQ-531.

Adverse event burden in older patients with CLL receiving bendamustine plus rituximab or ibrutinib regimens: Alliance A041202.

Ibrutinib has superior progression-free survival compared with bendamustine plus rituximab (BR) in older CLL patients, however, differences in treatment duration, six monthly BR cycles versus continuous ibrutinib, complicate adverse event (AE) comparisons. We introduce the AE burden score (AEsc) to compare AEs, calculated for each patient by summing over products of reporting period length and grade for each all-cause grade 1-4 AE and dividing by the length of time over which AEs are assessed. A total of 176 patients received BR and 361 ibrutinib alone or with six cycles of rituximab. At 38 months median follow-up, 64% remained on ibrutinib. Median AEsc was higher with BR versus ibrutinib in the first six cycles (7.2 versus 4.9, p < 0.0001). Within ibrutinib arms, median AEsc decreased significantly to 3.7 after six cycles (p < 0.0001). 10% and 14% of BR and ibrutinib patients discontinued treatment for AEs. In ibrutinib arms, cumulative incidence of grade 3 or higher atrial fibrillation, hypertension, and infection (AEs of clinical interest) at 12 months was 4.5%, 17.5%, and 12.8%, respectively, and increased more slowly thereafter to 7.7%, 25.4%, and 20.5% at 36 months. Analytical tools including the AEsc and cumulative incidence of AEs can help to better characterize AE burden over time. ClinicalTrials.gov identifier: NCT01886872.

A phase 3, randomized study of ofatumumab combined with bendamustine in rituximab-refractory iNHL (COMPLEMENT A + B study).

The standard of care for indolent non-Hodgkin lymphoma (iNHL) is rituximab, an anti-CD20 antibody, with/without chemotherapy. However, multiple relapses are common in these patients. This phase 3, randomized study compared outcomes of a combination of ofatumumab (a second-generation anti-CD20 antibody) and bendamustine, with bendamustine alone in patients unresponsive to prior rituximab-based treatment. Overall, 346 patients were randomized to receive either the combination or bendamustine alone. Bendamustine was given for ≤8 cycles and ofatumumab for ≤12 cycles. The primary end-point was progression-free survival (PFS) after 215 protocol-defined events assessed by independent review committee (IRC). Median IRC-assessed PFS was 16·7 and 13·8 months in the combination and monotherapy arms respectively [hazard ratio (HR) = 0·82; P = 0·1390]. Median overall survival (OS) was 58·2 and 51·8 months in the combination and monotherapy arms respectively (HR = 0·89, P = 0·4968). The safety profile was consistent with previous reports. Overall, 73% and 80% of patients in the combination and monotherapy arms, respectively, experienced a ≥grade 3 adverse event. The study did not meet its primary end-point. No significant improvement in PFS and OS was seen with the combination of ofatumumab and bendamustine as compared with bendamustine alone in rituximab-refractory iNHL (NCT01077518).

Rare lymphomas in routine practice - Treatment and outcome in marginal zone lymphoma in the prospective German Tumour Registry Lymphatic Neoplasms.

Owing to its heterogeneity and rarity, management of disseminated marginal zone B-cell lymphoma (MZL) remains largely understudied. We present prospective data on choice of systemic treatment and survival of patients with MZL treated in German routine practice. Of 175 patients with MZL who had been documented in the prospective clinical cohort study Tumour Registry Lymphatic Neoplasms (NCT00889798) collecting data on systemic treatment, 58 were classified as extranodal MZL of mucosa-associated lymphoid tissue (MALT) and 117 as non-MALT MZL. We analyzed the most commonly used first-line and second-line chemo(immuno)therapies between 2009 and 2016 and examined objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and prognostic factors for survival. Compared to patients with MALT MZL, those with non-MALT MZL more often presented with bone marrow involvement (43% vs. 14%), Ann Arbor stage III/IV (72% vs. 57%) and were slightly less often in good general condition (ECOG = 0; 41% vs. 47%). In German routine practice, rituximab-bendamustine for a median of 6 cycles was the most frequently used first-line (76%) and second-line treatment (36%), with no major differences between MZL subtypes. The ORR for patients encompassing any positive response was 81%. For patients with MALT and non-MALT MZL, respectively, 5-years PFS was 69% (95% CI 52%-81%) and 66% (95% CI 56%-75%), 5-years OS 79% (95% CI 65%-89%) and 75% (95% CI 66%-83%). Cox proportional hazards models showed a significantly increased risk of mortality for higher age in all patient groups. Our prospective real world data give valuable insights into the management and outcome of non-selected patients with MZL requiring systemic treatment and can help optimize therapy recommendations.

A phase 2 study of polatuzumab vedotin + bendamustine + rituximab in relapsed/refractory diffuse large B-cell lymphoma.

Polatuzumab vedotin (pola) is a CD79b-targeted antibody-drug conjugate delivering a potent antimitotic agent (monomethyl auristatin E) to B cells. This was an open-label, single-arm study of pola 1.8 mg/kg, bendamustine 90 mg/m2 , rituximab 375 mg/m2 (pola + BR) Q3W for up to six cycles in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who received ≥1 prior line of therapy and were ineligible for autologous stem cell transplantation (ASCT) or experienced treatment failure with prior ASCT. Primary endpoint was complete response rate (CRR) at the end of the treatment (EOT) by positron emission tomography-computed tomography (PET-CT) using modified Lugano Response Criteria. Secondary endpoints included efficacy, safety, and pharmacokinetics. Thirty-five patients (median age 71 [range 46-86] years) were enrolled. Twenty-three (66%) patients had refractory disease, and 23 (66%) had ≥2 prior lines of therapy. At a median follow-up of 5.4 (0.7-11.9) months, patients received a median of five treatment cycles. CRR was 34.3% (95% confidence interval [CI] 19.1-52.2) at EOT. Overall response rate was 42.9% at EOT, and median progression-free survival was 5.2 months (95% CI 3.6-not evaluable). Median overall survival was not reached. No fatal adverse events (AEs) were observed. Grade 3-4 AEs were mainly hematological: anemia (37%), neutropenia (31%), white blood cell count decreased (23%), thrombocytopenia/platelet count decreased/neutrophil count decreased (20% each), and febrile neutropenia (11%). Grade 1-2 peripheral neuropathy (PN; sensory and/or motor) was reported in 14% of patients; there were no ≥grade 3 PN events. This study (JapicCTI-184048) demonstrated the efficacy and safety of pola + BR in Japanese patients with R/R DLBCL who were ineligible for ASCT.

Low absolute lymphocyte count is a poor prognostic factor for untreated advanced follicular lymphoma treated with rituximab plus bendamustine: results of the prospective phase 2 CONVERT trial.

The aim of this trial is to evaluate the utility of rituximab-bendamustine (R-B) for untreated advanced follicular lymphoma (FL) showing non-optimal response (nOR) to R-CHOP, and to identify clinical prognostic factors for FL patients receiving R-B. Patients who failed to achieve complete response/complete response unconfirmed (CR/CRu) [nOR-group] after 2 cycles of R-CHOP subsequently received 6 cycles of R-B. The primary endpoint was the 3-year progression-free survival (PFS) rate. Secondary endpoints included determination of prognostic factors. Fifty-six patients initially received R-CHOP, 43/56 patients (76.8%) were judged as nOR, and 33/43 patients (76.7%) completed 6 cycles of R-B. At a median follow-up of 50.6 months in the nOR-group, the 3-year PFS rate was 69.0%, and the 3-year overall survival (OS) rate was 92.7%. The most common toxicities associated with R-B were grade 3-4 lymphopenia (93.0%) and neutropenia (74.4%), both of which were manageable. A multivariate analysis including dose intensity, serum soluble interleukin-2 receptor, and FL international prognostic index-2 revealed low absolute lymphocyte count (< 869/µL) at diagnosis was an independent poor prognostic factor for both PFS and OS in the R-B-treated nOR-group. This result was further confirmed in validation cohorts including R-B-treated de novo (n = 40) and relapsed (n = 49) FL patients.

Cutaneous involvement by T-cell prolymphocytic leukemia presenting as livedoid vasculopathy.

T-cell prolymphocytic leukemia (T-PLL) is a rare, aggressive neoplasm derived from post-thymic T-cells. Patients are typically middle aged with a slight male predominance who present with a high white blood cell count, hepatosplenomegaly, lymphadenopathy, and other symptoms typically associated with leukemia. Although cutaneous involvement has been reported in up to 30% of cases of T-PLL, to our knowledge, none have presented with a presentation resembling livedoid vasculopathy. In the correct clinical context, an underlying hematolymphoid neoplasm should be included in the differential diagnosis of a patient presenting with livedoid vasculopathy.