Real-world experience among patients with relapsed/refractory mantle cell lymphoma after Bruton tyrosine kinase inhibitor failure in Europe: The SCHOLAR-2 retrospective chart review study

Mantle cell lymphoma (MCL) after relapse is associated with poor prognosis. No standard of care exists and available evidence for treatments is limited, particularly in patients who fail Bruton tyrosine kinase inhibitor (BTKi) therapy. This multicentre retrospective chart review study, SCHOLAR-2, addresses this knowledge gap and reports on data collected from 240 patients with relapsed/refractory MCL in Europe who were treated with BTKi-based therapy between July 2012 and July 2018, and had experienced disease progression while on BTKi therapy or discontinued BTKi therapy due to intolerance. The median overall survival (OS) from initiation of first BTKi therapy was 14.6 months (95% confidence interval [CI] 11.6–20.0) in the overall cohort, 5.5 months (95% CI 3.9–8.2) in 91 patients without post-BTKi therapy, and 23.8 months (95% CI 18.9–30.1) in 149 patients who received post-BTKi therapy (excluding chimeric antigen receptor T-cell treatment). In the latter group, patients received a median of one (range, one to seven) line of post-BTKi therapy, with lenalidomide-containing regimens and bendamustine plus rituximab being the most frequently administered; the median OS from initiation of first post-BTKi therapy was 9.7 months (95% CI 6.3–12.7). These results provide a benchmark for survival in patients with R/R MCL receiving salvage therapy after BTKi failure

Durable response with single-agent acalabrutinib in patients with relapsed or refractory mantle cell lymphoma

Bruton tyrosine kinase (BTK) inhibitors have greatly improved the spectrum of treatment options in mantle cell lymphoma (MCL) [1–4]. Acalabrutinib is a highly selective, orally administered, and potent BTK inhibitor with limited off-target activity [5]. Acalabrutinib was approved in 2017 by the US Food and Drug Administration for the treatment of relapsed/refractory MCL based on clinical data from the open-label, multicenter, phase 2 ACE-LY-004 study of acalabrutinib 100 mg twice daily [1]. Here, we present updated results from the ACE-LY-004 study after a median 26-month follow-up. Eligibility criteria and study design were published previously (Supplementary methods) [1]. Analysis of minimal residual disease (MRD) was conducted after complete response (CR) or partial response (PR) was achieved using the quantitative ClonoSEQ next-generation sequencing (5 × 10−6 ) assay (Adpative Biotechnologies, Seattle, WA, USA) in consenting patients with available paired archival tumor and whole blood samples. Data are updated as of February 12, 2018

Subcutaneous Rituximab-MiniCHOP compared with subcutaneous Rituximab-MiniCHOP plus Lenalidomide in diffuse large B-Cell lymphoma for patients age 80 years or older.

peer reviewedPURPOSE The prognosis of elderly patients with diffuse large B-cell lymphoma (DLBCL) is worse than that of young patients. An attenuated dose of chemotherapy—cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-miniCHOP)—is a good compromise between efficacy and safety in very elderly patients. In combination with R-CHOP (R2-CHOP), lenalidomide has an acceptable level of toxicity and may mitigate the negative prognosis of the non–germinal center B-cell–like phenotype. The Lymphoma Study association conducted a multicentric, phase III, open-label, randomized trial to compare R-miniCHOP and R2- miniCHOP. PATIENTS AND METHODS Patients of age 80 years or older with untreated DLBCL were randomly assigned into the R-miniCHOP21 group or the R2-miniCHOP21 group for six cycles and stratified according to CD10 expression and age. The first cycle of rituximab was delivered by IV on D1 after a prephase and then delivered subcutaneously on D1 of cycles 2-6. Lenalidomide was delivered at a dose of 10 mg once daily on D1-D14 of each cycle. The primary end point was overall survival (OS). RESULTS A total of 249 patients with new DLBCL were randomly assigned (127 R-miniCHOP and 122 R2- miniCHOP). The median age was 83 years (range, 80-96), and 55% of the patients were classified as non-GCB. The delivered dose for each R-miniCHOP compound was similar in both arms. Over a median follow-up of 25.1 months, the intention-to-treat analysis revealed that R2-miniCHOP did not improve OS (2-year OS 66% in R-miniCHOP and 65.7% in R2-miniCHOP arm, P5 .98) in the overall population or in the non-GCB population. Grade 3-4 adverse events occurred in 53% of patients with R-miniCHOP and in 81% of patients with R2- miniCHOP. CONCLUSION The addition of lenalidomide to R-miniCHOP does not improve OS. Rituximab delivered subcutaneously was safe in this population

Durable response with single-agent acalabrutinib in patients with relapsed or refractory mantle cell lymphoma

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Eyelids metastases from uveal melanoma: clinical and histopathologic features of two cases and literature review.

To report the clinical and histopathologic features of two cases of eyelids metastases from uveal melanoma diagnosed in a metachronous and synchronous fashion. Monocentric retrospective case series of histopathologically proven eyelids metastases from uveal melanoma at our institution. Two patients were presented to our hospital for upper eyelids pigmented and firm lesions. Patient 1 had an history of left uveal melanoma treated conservatively with proton beam therapy 5 years earlier. Examination revealed bilateral upper eyelids lesions. Patient 2 had no malignancy history but was incidentally diagnosed with a cerebral nodule few months earlier. Examination revealed a right upper eyelid nodule and a previously unknown right uveal melanoma. Excisional biopsy was performed for both patients. Pathological assessment allowed the presence of melanoma cells. The lack of BAP1 nuclear expression on immunohistochemistry as well as the absence of cutaneous or mucosal melanoma were consistent with an uveal origin. Diffuse metastatic spread was noted for both patients. Systemic therapies were prescribed. Patient 1 died from metastatic spread (62 months and 4 months after uveal melanoma diagnosis and eyelids metastases removal, respectively) whereas patient 2 was still alive (14 months follow up). Eyelids metastases from uveal melanoma is an exceptional finding. Excisional biopsy and pathological assessment are of main importance to confirm the diagnosis and to identify genetic mutations for further targeted therapies. Currently, prognosis remains poor

Orbital exenteration and conjunctival melanoma: a 14-year study at the Jules Gonin Eye Hospital.

To report our 14-year experience with orbital exenteration and assess risk factors for poor prognosis by focusing on conjunctival melanoma. A retrospective study was conducted in our tertiary care centre (Jules Gonin Eye Hospital, Lausanne, Switzerland) between 2003 and 2017. Inclusion criteria were patients aged ≥18 years with a follow-up >12 months, without metastatic spread at the time of surgery. Data recorded were age, gender, tumour histology, surgical technique, postoperative complications, surgical margin status, local recurrence, postoperative radiation beam therapy and metastatic status. Twenty-five patients with a mean age of 63.2 years (38-92) were included. Conjunctival melanoma was the most frequently identified tumour (n = 14, 56%) followed by conjunctival squamous cell carcinoma (n = 4, 16%), sebaceous carcinoma (n = 3, 12%), choroidal melanoma (n = 2, 8%) and basal cell carcinoma (n = 2, 8%). Eighteen tumours (72%) originated from the conjunctival tissue. Clear surgical margins were achieved in 21 (84%) patients. Fourteen (56%) patients experienced distant metastases and died from metastatic spread after a mean follow-up of 52.3 months (6-120). The 1-, 3- and 5-year overall survival (OS) was 96%, 72% and 60%, respectively. In the univariate analysis, positive surgical margins, local recurrence and metachronous metastases were associated with a decreased OS (p = 0.002, p = 0.005 and p = 0.007, respectively). In the multivariate analysis, positive surgical margins and metachronous metastases were also associated with a decreased OS (p = 0.02 and p = 0.042, respectively). Conjunctival melanoma was not associated with a poorer prognosis (p = 0.280). Free surgical margins are needed to increase OS. To achieve clearer surgical margins, neoadjuvant targeted therapies/immunotherapies may be considered

Evolution du taux de gammaglobulines chez les patients atteints de leucémie lymphoïde chronique traités par ibrutinib

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