Real-world effectiveness of ixazomib combined with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: the REMIX study.

Ixazomib (IXA) is an oral proteasome inhibitor (PI) used in combination with lenalidomide and dexamethasone (IXA-Rd) for patients with relapsed and/or refractory multiple myeloma (RRMM). The REMIX study is one of the largest prospective, real-world analysis of the effectiveness of IXA-Rd in the setting of RRMM. Conducted in France between August 2017 and October 2019, the REMIX study, a non-interventional prospective study, included 376 patients receiving IXA-Rd in second line or later and followed for at least 24 months. Primary endpoint was the median progression-free survival (mPFS). Median age was 71 years (Q1-Q3 65.0 - 77.5) with 18.4% of participants older than 80 years. IXA-Rd was initiated in L2, L3 and L4 + for 60.4%, 18.1% and 21.5%, respectively. mPFS was 19.1 months (95% CI [15.9, 21.5]) and overall response rate (ORR) was 73.1%. mPFS was 21.5, 21.9 and 5.8 months in patients receiving IXA-Rd as L2, L3, L4 + respectively. Among patients receiving IXA-Rd in L2 and L3, mPFS was similar for patients previously exposed to lenalidomide (19.5 months) than for those lenalidomide naive (not exposed, 22.6 months, p = 0.29). mPFS was 19.1 months in patients younger than 80 years and 17.4 months in those 80 years or older (p = 0.06) with similar ORR (72.4% and 76.8%) in both subgroups. Adverse events (AEs) were reported in 78.2% of patients including 40.7% of treatment-related AE. IXA discontinuation was due to toxicity in 21% of patients. To conclude, the results of the REMIX study are consistent with the results of Tourmaline-MM1 and confirm the benefit of IXA-Rd combination in real life. It shows the interest of IXA-Rd in an older and frailer population, with an acceptable effectiveness and tolerance.

Acquired factor V inhibitor: Success of steroids in a patient with primary sclerosing cholangitis, ulcero haemorragic rectocolitis, biological Biermer's disease.

We report the case of a 43-years-old Turkish man with acquired deficiency of factor V (FV) diagnosed in a usual screening before a (recto) colonoscopy. In the biologic explorations, activated partial prothrombin time (APTT) was abnormally high and prothrombin time (PT) was low 18IU/dL with no anticoagulant drugs (the PT was normal 6 months ago). The controlled level of factor V was 3IU/dL with FV antibodies (9 Bethesda Units/mL). This patient had a previous history of primary sclerosing cholangitis (2000) and ulcero haemorrhagic rectocolitis (2002) and a fortuitous biological Biermer's disease was revealed. Corticosteroids were prescribed at 1mg/kg/day with decreasing during 6 months, patient had gradual regression of the caused bleeding and FV became greater than 90%, F V antibodies decreased to less than 0.7 Bethesda Units/mL. This case illustrates the presence of FV inhibitor in an autoimmune gastrointestinal context with regression of clinical (caused) signs and antibodies with corticosteroids.

Diagnosis and immediate treatment of acquired von Willebrand syndrome revealed by recurrent cerebral hemorrhage.

We report the case of a French woman with acquired von Willebrand syndrome who presents recurrent subarachnoid and intra-cerebral hemorrhage since 2012. She had no family or personal bleeding history. In the biologic explorations, APTT was abnormally high with no anticoagulant drugs (it was normal, historically). Two monoclonal IgG and IgM kappa proteins were detected without any lymphoproliferative disorder. Intravenous infusion of immunoglobulin is very effective in AVWS with immunoglobulin G monoclonal gammapathie of undetermined significance. We had a satisfactory correction of coagulation factors for about 30 days. The exploration of APTT is surely essential for the diagnosis and treatment.

Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion.

After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA.

Acute myocardial ischemia after high-dose therapy with BEAM regimen.

We describe a case of acute myocardial ischemia following carmustine treatment during the BEAM regimen. Despite this, full completion of the autologous peripheral stem-cell transplant was possible.

Primary breast lymphoma: a report of 20 cases.

Limited data are available concerning treatment and outcome of primary lymphoma of the breast (PLB), especially after CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, prednisone) chemotherapy. We retrospectively reviewed 20 consecutive cases of localized PLB seen at our institution over a 20 year period. All PLB were of B-cell origin: treatment was CHOP or a CHOP-like regimen in all patients. Sixteen of the 20 patients achieved complete remission (CR) and two achieved partial remission (> 75% tumour regression). Two patients had progressive disease on therapy. With a median follow-up of 54 months, six patients relapsed after 8-66 months. Two of the relapses involved the central nervous system (CNS) (isolated in one case, associated with other sites of relapse in the other). The two patients who achieved partial remission also had progression in the CNS, 4 and 8 months after the end of CHOP chemotherapy. All four patients have died as a result of their disease 3, 6, 10 and 13 months after CNS relapse. Of the 16 centroblastic diffuse large B-cell lymphoma (DLCL), three had CNS disease at relapse. We also observed three (15%) controlateral breast relapses. Thirteen of the initial 20 patients are alive in CR, six patients have died as a result of their lymphoma and one of unrelated disease. In conclusion, we observed a high incidence of CNS relapse in this group of localized extranodal lymphoma, strongly suggesting that CNS prophylaxis should be associated with systemic chemotherapy in localized PLB.

Blindness following gastrointestinal haemorrhage.

Loss of vision is a rare but well known complication of distant and recurrent haemorrhage. It shares a poor prognosis, with only 10-14% of cases likely to make a complete recovery. Visual symptoms, due to ischaemic anterior optic neuropathy, vary from blurred vision to complete loss of vision in one or both eyes. The pathogenesis of such ischaemia remains unclear. Gastrointestinal bleeding seems to be the leading cause of loss of vision secondary to haemorrhage. However, complete and permanent blindness following gastrointestinal bleeding has rarely been reported. We report the case of a 51 -year-old woman who complained of complete blindness following blood loss, secondary to peptic ulcer, and discuss the pathogenesis of such a complication.