Carfilzomib, lenalidomide, dexamethasone (KRD) in BTKi relapsed or refractory mantle cell lymphoma: A phase II study from Fondazione Italiana Linfomi.

Mantle cell lymphoma (MCL) is a rare lymphoproliferative neoplasm considered incurable, with a median survival of 3-5 years. In recent years, Bruton's tyrosine kinase inhibitors (BTKi) have been introduced, demonstrating high therapeutic activity. However, the prognosis for MCL patients failing ibrutinib therapy is particularly poor, with a survival expectation of a few months. In this phase II trial, we assessed the efficacy and safety of the carfilzomib-lenalidomide-dexamethasone (KRD) combination in MCL patients who were relapsed/refractory (R/R) or intolerant to BTKi and in need of treatment. The primary objective of the study was to evaluate the antitumor efficacy of the KRD combination in terms of 12-month overall survival (12-month OS). From September 2019 to December 2020, 16 patients were enrolled from 11 Italian centers. After a median follow-up of 2.37 months (95% CI 0.92-6.47), the 12-month OS was 13%. The rate of grade 3-4 adverse events (AEs) was 35%, and the overall response rate (ORR) was 19%. These results led to the premature termination of enrollment, as defined in the protocol stopping rules. The efficacy of the KRD combination in advanced-stage MCL patients who are R/R to BTKi is unsatisfactory and too toxic.

Genetic and phenotypic attributes of splenic marginal zone lymphoma.

Splenic marginal zone B-cell lymphoma (SMZL) is a heterogeneous clinico-biological entity. The clinical course is variable, multiple genes are mutated with no unifying mechanism, and essential regulatory pathways and surrounding microenvironments are diverse. We sought to clarify the heterogeneity of SMZL by resolving different subgroups and their underlying genomic abnormalities, pathway signatures, and microenvironment compositions to uncover biomarkers and therapeutic vulnerabilities. We studied 303 SMZL spleen samples collected through the IELSG46 multicenter international study (NCT02945319) by using a multiplatform approach. We carried out genetic and phenotypic analyses, defined self-organized signatures, validated the findings in independent primary tumor metadata and in genetically modified mouse models, and determined correlations with outcome data. We identified 2 prominent genetic clusters in SMZL, termed NNK (58% of cases, harboring NF-κB, NOTCH, and KLF2 modules) and DMT (32% of cases, with DNA-damage response, MAPK, and TLR modules). Genetic aberrations in multiple genes as well as cytogenetic and immunogenetic features distinguished NNK- from DMT-SMZLs. These genetic clusters not only have distinct underpinning biology, as judged by differences in gene-expression signatures, but also different outcomes, with inferior survival in NNK-SMZLs. Digital cytometry and in situ profiling segregated 2 basic types of SMZL immune microenvironments termed immune-suppressive SMZL (50% of cases, associated with inflammatory cells and immune checkpoint activation) and immune-silent SMZL (50% of cases, associated with an immune-excluded phenotype) with distinct mutational and clinical connotations. In summary, we propose a nosology of SMZL that can implement its classification and also aid in the development of rationally targeted treatments.

Real-world use of thrombopoietin receptor agonists in older patients with primary immune thrombocytopenia.

The efficacy and safety of thrombopoietin receptor agonists (TRAs) in older patients with primary immune thrombocytopenia (ITP) are unknown. We investigated TRA response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROTs) in 384 patients with ITP aged ≥60 years. After 3 months, 82.5% and 74.3% of eltrombopag- and romiplostim-treated patients, respectively, achieved a response; 66.7% maintained the response (median follow-up, 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; although no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. Thirty-four major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, while on TRAs and were associated with thrombosis history (subdistribution hazard ratio, 2.04, P = .05) and platelet count <20 × 109/L (subdistribution hazard ratio, 1.69; P = .04), respectively, at TRA start. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but 1 during persisting TRA treatment (incidence rate, 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRAs; 53 (13.8%) patients maintained SROTs, which were associated with TRA discontinuation in complete response (P < .001). Very old age (≥75 years; 41.1%) was associated with the more frequent start of TRAs in the persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in older patients with ITP, with no fatal hemorrhages and with SROTs in a significant portion of patients. Caution is warranted in patients with a history of thrombosis, and a careful risk/benefit balance should be considered.

Eltrombopag second-line therapy in adult patients with primary immune thrombocytopenia in an attempt to achieve sustained remission off-treatment: results of a phase II, multicentre, prospective study.

Up to 30% immune thrombocytopenia (ITP) patients achieve a sustained remission off-treatment (SROT) after discontinuation of thrombopoietin receptor agonists (TPO-RAs). Factors predictive of response are lacking. Patients aged ≥18 years with newly diagnosed or persistent ITP were treated with eltrombopag for 24 weeks. Primary end-point was SROT: the proportion of responders that were able to taper and discontinue eltrombopag maintaining the response during a period of observation (PO) of six months. Secondary end-points included the association between some immunological parameters (TPO serum levels, cytokines and lymphocyte subsets) and response. Fifty-one patients were evaluable. Primary end-point was achieved in 13/51 (25%) treated patients and 13/34 (38%) patients who started the tapering. Baseline TPO levels were not associated with response at week 24 nor with SROT. Higher baseline levels of IL-10, IL-4, TNF-α and osteopontin were negative factors predictive of response (P = 0·001, 0·008, 0·02 and 0·03 respectively). This study confirms that SROT is feasible for a proportion of ITP patients treated with eltrombopag. Some biological parameters were predictive of response.

Eltrombopag for immune thrombocytopenia secondary to chronic lymphoproliferative disorders: a phase 2 multicenter study.

Immune thrombocytopenia (ITP) secondary to chronic lymphoproliferative disorders (LPDs) is poorly responsive to conventional treatments. We conducted a multicenter phase 2 prospective 24-week study in 18 patients with ITP secondary to LPDs to assess the safety and efficacy of eltrombopag. Responsive patients entered an extension study for up to 5 years. For inclusion, patients should not require cytotoxic treatment and should have a platelet count <30 × 109/L or have symptoms of bleeding. Eltrombopag was initiated at 50 mg/day, with a maximum of 150 mg/day. The primary end point was platelet response after 4 weeks. Median age was 70 years (range, 43-83 years), and 14 patients had chronic lymphocytic leukemia, 2 had classic Hodgkin lymphoma, and 2 had Waldenström macroglobulinemia. All patients had received previous ITP treatments. Response rate at week 4 was 78% (95% confidence interval [CI], 58%-97%), with 50% of patients having a complete response (CR) (95% CI, 43%-57%); respective results at week 24 were 59% (95% CI, 36%-82%) with 30% reaching a CR (95% CI, 8%-52%). Median exposure to eltrombopag was 16 months; median dose at week 4 was 50 mg/day (range, 25-100 mg/day), and at week 24, it was 50 mg/day (range, 25-150 mg/day). No grade >2 adverse events were reported. Eltrombopag is active and well tolerated in ITP secondary to LPDs. This trial was registered at www.clinicaltrials.gov as #NCT01610180.

Rituximab in the treatment of immune thrombocytopenia: what is the role of this agent in 2019?

The use of rituximab for the treatment of immune thrombocytopenia was greeted enthusiastically: it led to up to 60% response rates, making it, nearly 20 years ago, the main alternative to splenectomy, with far fewer side effects. However, long-term follow-up data showed that only 20-30% of patients maintained the remission. No significant changes have been registered using different dose schedules and timing of administration, while the combination with other drugs seemed promising. Higher response rates have been observed in young women before the chronic phase, but apart from that, other clinical factors or biomarkers predictive of response are still lacking. In this review we examine the historical and current role of rituximab in the management of immune thrombocytopenia, 20 years after its first use for the treatment of autoimmune diseases.

Successful treatment and FDG-PET/CT monitoring of HHV-6 encephalitis in a non-neutropenic patient: case report and literature review.

Human herpesvirus (HHV)-6 reactivation is associated with severe forms of encephalitis among patients undergoing hematopoietic stem cell transplantation. Cases in non-neutropenic patients are uncommon. The efficacy of ganciclovir and other compounds that are used for the treatment of HHV-6 encephalitis remains suboptimal and linked to toxicity. Valganciclovir, the oral prodrug of ganciclovir, could be practical to treat outpatients, but it is not commonly used for severe cases. We report a case of HHV-6 encephalitis in a non-neutropenic patient successfully treated with valganciclovir and undergoing therapeutic drug monitoring in plasma and in the cerebrospinal fluid. Resolution of infectious foci was documented by cerebral MRI and F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). A review of the literature on HHV-6 encephalitis is also reported.

Rituximab in immune thrombocytopenia: gender, age, and response as predictors of long-term response.

OBJECTIVES: To evaluate the efficacy of a salvage treatment with rituximab (RTX) in adults with primary immune thrombocytopenia (ITP), in terms of short-term response and long-term response (LTR, i.e., probability to achieve and maintain response) and to identify biological and clinical predictors of response. METHODS: We retrospectively evaluated the outcome of patients with primary ITP treated with standard dosage RTX (375 mg/m2 × 4) as salvage therapy in five Italian centers. One hundred and three patients, median age of 46 yr, were included. The median period of observation was 59 months. RESULTS: Response (R) and complete response (CR) were documented in 57 (55%) and 37 (36%) patients, respectively. Patients younger than 40 yr had a higher probability to achieve CR (P = 0.025). Younger women (age < 40 yr) had a significantly higher probability to achieve R and CR (P = 0.039 and P = 0.009, respectively). The estimated LTR rate was 36% and 31% after 48 and 72 months, respectively; female sex (P = 0.033) and younger age (P = 0.021) were associated with better LTR. Younger women had the highest LTR rate (P = 0.006). Response duration was associated with the obtainment of CR after RTX (CR vs. partial response, P = 0.002). CONCLUSIONS: The effect of RTX salvage treatment appears higher in younger women, with LTR rate possibly approaching that of splenectomy.

Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results.

BACKGROUND: The role of consolidation radiotherapy in primary mediastinal B-cell lymphoma (PMBCL) patients is controversial. METHODS: The IELSG37 trial, a randomized non-inferiority study, aimed to assess whether irradiation can be omitted in PMBCL patients with complete metabolic response (CMR) after induction immunochemotherapy. Primary endpoint was progression-free survival (PFS) at 30 months post-randomization. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a non-inferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomized. RESULTS: The observed events were considerably lower than expected, therefore, primary endpoint analysis was conducted when ≥95% of patients were followed for ≥30 months. Of 545 patients enrolled, 268 were in CMR after induction and were randomized to observation (n=132) or radiotherapy (n=136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95%CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95%CI, -0.97% to 7.46%). The 5-year overall survival was 99% in both arms.Non-randomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomized patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). CONCLUSIONS: This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation.

Nationwide Survey on the Use of Thrombopoietin Receptor Agonists (TPO-RA) for the Management of Immune Thrombocytopenia in Current Clinical Practice in Italy.

Background: Two thrombopoietin receptor agonists (TPO-RA), romiplostim and eltrombopag, are currently widely adopted as second-line ITP therapy even in the absence of robust evidence on their comparative advantages over rituximab or splenectomy or their preferential use in some specific clinical contexts. Methods: An online survey was distributed between May 2021 and June 2021 to collect standardized information on TPO-RA use in Italy. Results: Eighty-eight hematologists from 79 centers completed the survey. Eighty-four percent would use TPO-RA earlier than formally indicated, without a preference for young or elderly in 82% of respondents. No clear preference for either romiplostim or eltrombopag was indicated. Seventy-two percent would use TPO-RA in young patients aiming at a complete response followed by tapering, a strategy considered by only 16% in the elderly. Switching between the two agents was considered appropriate in case of insufficient response or intolerance. Tapering schedule by reducing the dosage and prolonging the intervals between administrations was preferred by 73% of respondents. TPO-RA was considered a risk factor for thrombosis by only 35%, and 94% would administer TPO-RA in elderly patients also in the presence of other thrombotic risk factors. Thirty-three percent of respondents would withdraw TPO-RA in case of thrombosis. The TPORA administration has been reported to be preferred over anti-CD20 or splenectomy by about half of the participants due to the ongoing COVID-19 pandemic. Conclusions: Significant discrepancies in TPO-RA use emerged from the survey, and participants would appreciate consensus-based specific guidance on the practical use of TPO-RA.

Serological and cellular response to mRNA-SARS-CoV2 vaccine in patients with hematological lymphoid malignancies: Results of the study "Cervax".

messenger RNA (mRNA)-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccines such as BNT162b2 became available in late 2020, but hematological malignancy patients (HM pts) were not evaluated in initial registration trials. We hereby report the results of a prospective, unicentric, observational study Response to COVID-19 Vaccination in hEmatological malignancies (CERVAX) developed to assess the postvaccine serological and T-cell-mediated response in a cohort of SARS-CoV2-negative HM pts vaccinated with BNT162b2. Patients with lymphomas [non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)], chronic lymphocytic leukemia (CLL), and multiple myeloma (MM); off-therapy for at least 3 months; in a watch-and-wait program; or in treatment with ibrutinib, venetoclax, and lenalidomide were included. Different time points were considered to assess the serological response to the vaccine: before the second dose (T1), at 3-6-12 months after the first dose (T2-3-4, respectively). Since March 2021, 39 pts have been enrolled: 15 (38%) NHL, 12 (31%) CLL, and 12 (31%) MM. There were 13 of the 39 pts (33%) seroconverted at T1; an increase of the serological response was registered after the second dose (T2) (22/39 pts, 56%) and maintained after 6 months (22/39 pts, 56%) and 12 months (24/39 pts, 61%) from the first dose (T3-T4, respectively). Non-serological responders at T4 were 7/39 (18%): 0/15 NHL, 1/12 MM (8%), and 6/12 CLL (50%). All of them were on therapy (one lenalidomide, three ibrutinib, and three venetoclax). SARS-CoV2-reactive T-cell analysis (interferon gamma release assays) was available since June 2022 and was evaluated at 12 months (T4) from the first dose of vaccine in 31/39 pts (79%). T-cell-mediated-responders were 17/31 (55%): most of them were NHL and MM (47%, 41% and 12% for NHL, MM, and CLL, respectively). Both serological and T-cell non-responders were represented by pts on active therapy (venetoclax/ibrutinib). During the period of observation, eight (20.5%) pts developed mild SARS-CoV2 infection; no coronavirus disease 19 (COVID-19)-related deaths or hospitalizations were registered. In conclusion, in our cohort of lymphoproliferative pts receiving BNT162b2, CLL diagnosis and venetoclax/ibrutinib seem to be related with a lower humoral or T-mediated response. Nevertheless, the efficacy of mRNA vaccine in HM pts and the importance to continue the vaccine program even in non-responders after the first dose are supported in our study by demonstrating that a humoral and T-cell-mediated seroconversion should be observed even in the subsets of heavily immunocompromised pts.

Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: the Fondazione Italiana Linfomi MCL0208 trial.

In the Fondazione Italiana Linfomi MCL0208 phase 3 trial, lenalidomide maintenance (LEN) after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL) improved progression-free survival (PFS) vs observation (OBS). The host pharmacogenetic background was analyzed to decipher whether single-nucleotide polymorphisms (SNPs) of genes encoding transmembrane transporters, metabolic enzymes, or cell-surface receptors might predict drug efficacy. Genotypes were obtained via real-time polymerase chain reaction of the peripheral blood germ line DNA. Polymorphisms of ABCB1 and VEGF were found in 69% and 79% of 278 patients, respectively, and predicted favorable PFS vs homozygous wild-type (WT) in the LEN arm was 3-year PFS of 85% vs 70% (P < .05) and 85% vs 60% (P < .01), respectively. Patients carrying both ABCB1 and VEGF WT had the poorest 3-year PFS (46%) and overall survival (76%); in fact, in these patients, LEN did not improve PFS vs OBS (3-year PFS, 44% vs 60%; P = .62). Moreover, the CRBN polymorphism (n = 28) was associated with lenalidomide dose reduction or discontinuation. Finally, ABCB1, NCF4, and GSTP1 polymorphisms predicted lower hematological toxicity during induction, whereas ABCB1 and CRBN polymorphisms predicted lower risk of grade ≥3 infections. This study demonstrates that specific SNPs represent candidate predictive biomarkers of immunochemotherapy toxicity and LEN efficacy after ASCT in MCL.

Case report: Long-lasting SARS-CoV-2 infection with post-COVID-19 condition in two patients with chronic lymphocytic leukemia: The emerging therapeutic role of casirivimab/imdevimab.

Post-coronavirus disease 2019 (post-COVID-19) condition, previously referred to as long COVID, includes a post-acute syndrome defined by the presence of non-specific symptoms occurring usually 3 months from the onset of the acute phase and lasting at least 2 months. Patients with chronic lymphocytic leukemia (CLL) represent a high-risk population for COVID-19. Moreover, the response to SARS-CoV-2 vaccination is often absent or inadequate. The introduction of monoclonal antibodies (mAbs) in the treatment landscape of COVID-19 allowed to reduce hospitalization and mortality in mild-moderate SARS-CoV-2 infection, but limited data are available in hematological patients. We here report the effective use of casirivimab/imdevimab (CI) in the treatment of two CLL patients with persistent infection and post-COVID-19 condition. Full genome sequencing of viral RNA from nasopharyngeal swabs was performed at the time of COVID-19 diagnosis and before the administration of CI. Both patients experienced persistent SARS-CoV-2 infection with no seroconversion for 8 and 7 months, respectively, associated with COVID symptoms. In both cases after the infusion of CI, we observed a rapid negativization of the nasal swabs, the resolution of post-COVID-19 condition, and the development of both the IgG against the trimeric spike protein and the receptor-binding domain (RBD) of the spike protein. The analysis of the viral genome in the period elapsed from the time of COVID-19 diagnosis and the administration of mAbs showed the development of new mutations, especially in the S gene. The genome variations observed during the time suggest a role of persistent SARS-CoV-2 infection as a possible source for the development of viral variants. The effects observed in these two patients appeared strongly related to passive immunity conferred by CI treatment permitting SARS-CoV-2 clearance and resolution of post-COVID-19 condition. On these grounds, passive anti-SARS-CoV-2 antibody treatment may represent as a possible therapeutic option in some patients with persistent SARS-CoV-2 infection.

Venetoclax in combination with hypomethylating agents in previously untreated patients with acute myeloid leukemia ineligible for intensive treatment: a real-life multicenter experience.

The addition of venetoclax to hypomethylating agents (HMA-V) improved the outcome of patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive treatment. The aim of our study was to confirm data reported in literature, in a real-life multicenter experience. We retrospectively evaluated 56 naïve AML patients who received HMA-V at 8 different collaborating Hematology Units in the North-East of Italy, from September 2018 to October 2020. Patients received azacitidine or decitabine at standard dose, adding venetoclax starting from cycle 1-3. The median time-to-response was 2 cycles and composite complete remission rate (CCR) was 67.9%. Thirteen out of 38 responders (34.2%) relapsed, with a median response duration of 13.7 months. Transfusion independence (TI) was obtained in 27 (87.0%) and 28 (90.3%) out of 31 patients for red blood cells and platelets, respectively. Median OS was 12.3 months (95% CI, 8.1-16.5), and median PFS was 11.3 months (95% CI, 4.6-17.9). Cytogenetic risk was the only variable impacting on survival, while no differences were observed stratifying patients by age, bone marrow blasts, WHO classification or type of HMA. In conclusion, our real-life multicenter experience indicates that HMA-V treatment allows achieving good response rates in naïve AML patients, ineligible for intensive chemotherapy.

Real-world Outcomes of Relapsed/Refractory Diffuse Large B-cell Lymphoma Treated With Polatuzumab Vedotin-based Therapy.

After FDA and EMA approval of the regimen containing polatuzumab vedotin plus rituximab and bendamustine (PolaBR), eligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients in Italy were granted early access through a Named Patient Program. A multicentric observational retrospective study was conducted focusing on the effectiveness and safety of PolaBR in everyday clinical practice. Fifty-five patients were enrolled. There were 26 females (47.3%), 32 patients were primary refractory and 45 (81.8%) resulted refractory to their last therapy. The decision to add or not bendamustine was at physician's discretion. Thirty-six patients underwent PolaBR, and 19 PolaR. The 2 groups did not differ in most of baseline characteristics. The final overall response rate was 32.7% (18.2% complete response rate), with a best response rate of 49.1%. Median disease-free survival was reached at 12 months, median progression-free survival at 4.9 months and median overall survival at 9 months, respectively. Overall, 88 adverse events (AEs) were registered during treatment in 31 patients, 22 of grade ≥3. Eight cases of neuropathy occurred, all of grades 1-2 and all related to polatuzumab. The two groups of treatment did not differ for effectiveness endpoints but presented statistically significant difference in AEs occurrence, especially in hematological AEs, in AEs of grade equal or greater than 3 and in incidence of neuropathy. Our data add useful information on the effectiveness of Pola(B)R in the setting of heavily pretreated DLBCL and may also suggest a better tolerability in absence of bendamustine without compromise of efficacy.

Case Report: Cardiac Involvement by Lymphoma: Rare but Heterogeneous Condition With Challenging Behaviors.

Cardiac lymphomas are rare extranodal lymphomas involving primarily and secondarily the heart and/or pericardium. Here we describe three cases of cardiac involvement from lymphoma with specific peculiarities: two primary cardiac Diffuse Large B-cell Lymphomas and one secondary involvement from Marginal Zone Lymphoma (MZL). The first case highlights the issue of early CNS relapse and the possible role for CNS prophylaxis; the second case demonstrates the difficulties of interpretation and possible mistakes of different radiologic techniques adopted to evaluate cardiac involvement by lymphoma during follow-up; the third is a unique case of MZL with cardiac involvement. Our aim is to share the findings observed in these cases putting them in relation with data from the literature.

Rituximab and Bendamustine (BR) Compared with Rituximab, Bendamustine, and Cytarabine (R-BAC) in Previously Untreated Elderly Patients with Mantle Cell Lymphoma.

BACKGROUND: Rituximab plus bendamustine (BR), and rituximab, bendamustine, and cytarabine (R-BAC) are well-known induction therapies in elderly patients with mantle cell lymphoma (MCL), according to clinical guidelines. However, a direct comparison between the two regimens has never been performed. METHODS: In this multicentre retrospective study, we compared the outcome of patients with newly diagnosed MCL, treated with BR or R-BAC. Primary endpoint was 2-year progression-free survival (PFS). Inclusion bias was assessed using a propensity score stratified by gender, age, MCL morphology, and MIPI score. RESULTS: After adjusting by propensity score, we identified 156 patients (53 BR, 103 R-BAC) with median age of 72 (53-90). Median follow-up was 46 months (range 12-133). R-BAC was administered in a 2-day schedule or with attenuated dose in 51% of patients. Patients treated with R-BAC achieved CR in 91% of cases, as compared with 60% for BR (p < 0.0001). The 2-year PFS was 87 ± 3% and 64 ± 7% for R-BAC and BR, respectively (p = 0.001). In terms of toxicity, R-BAC was associated with significantly more pronounced grade 3-4 thrombocytopenia than BR (50% vs. 17%). CONCLUSIONS: This study indicates that R-BAC, even when administered with judiciously attenuated doses, is associated with significantly prolonged 2-year PFS than BR in elderly patients with previously untreated MCL.

Immune checkpoint inhibitors in combination with radiotherapy as salvage treatment for relapsed/refractory classical Hodgkin lymphoma: A retrospective analysis in 12 patients.

The rate of complete remission (CR) with the anti-PD1 immune checkpoint inhibitors (ICI) nivolumab (N) and pembrolizumab (P) in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) is low (20-30%), and the majority of patients eventually relapse. One strategy to improve their outcome is to combine ICI with radiotherapy (ICI-RT), taking advantage of a supposed synergistic effect. We retrospectively collected data of 12 adult patients with R/R cHL treated with ICI-RT delivered during or within 8 weeks from the start or after the end of ICI. Median age at ICI-RT was 37 years, 50% had previously received an autologous stem cell transplantation (SCT) and 92% brentuximab vedotin. RT was given concurrently, before or after ICI in 4, 1 and 7 patients. Median RT dose was 30Gy, for a median duration of 22 days. Median number of ICI administrations was 15. Overall response and CR rate were 100% and 58%. Nine patients received subsequent SCT consolidation (7 allogeneic and 2 autologous). After a median follow-up of 18 months, 92% of patients were in CR. No major concerns about safety were reported. ICI-RT combination appears to be a feasible and highly active bridge treatment to transplant consolidation.