Isatuximab in combination with lenalidomide and dexamethasone in patients with high-risk smoldering multiple myeloma: Updated safety run-in results from the randomized phase 3 ithaca study

Background: Results from a randomized, Phase 3 study by the Spanish Myeloma Group (PETHEMA/GEM) previously showed that treatment with lenalidomide plus dexamethasone (Rd) may delay progression to active disease in patients (pts) with high-risk smoldering multiple myeloma (SMM), compared with observation. To further improve outcomes, addition of the anti-CD38 antibody isatuximab (Isa) to lenalidomide and dexamethasone (Isa-Rd) for the treatment of pts with high-risk SMM is being evaluated in the ongoing, randomized, multi-center, Phase 3 ITHACA study (NCT04270409). Initial findings from the safety run-in analysis of this trial have shown a manageable safety profile and encouraging, preliminary anti-myeloma activity. We now report updated safety and efficacy results from the safety run-in part of ITHACA at a median follow-up of 19.4 months. Methods: Pts were included in the study if they had been diagnosed within 5 years with SMM (per the International Myeloma Working Group [IMWG] criteria) and had high-risk SMM according to the Mayo '20-2-20' and/or updated PETHEMA model criteria. Pts who had received prior anti-myeloma treatment were not eligible. Enrolled pts received Isa 10 mg/kg IV on day (D) 1, 8, 15, and 22 in cycle (C) 1, D1 and D15 C2-12, D1 C13-36; plus R D1-21 (25 mg C1-9; 10 mg C10-24) and d weekly (40 mg, 20 mg for ≥75 yr-old pts C1-9; 20 mg C10-24). Cycle duration was 28 days. Safety evaluations included treatment-emergent AEs (TEAEs)/serious AEs and laboratory parameters, graded by NCI-CTCAE v5.0. Response was determined by IMWG criteria (2016). Mandatory imaging by MRI and/or low-dose whole-body CT/PET-CT, and assessments of minimal residual disease (MRD, by next-generation sequencing in pts with very good partial response [VGPR] or better), were performed at protocol-defined time points. The primary study objective for the safety run-in was to confirm the recommended dose of Isa in combination with Rd. Overall response rate (ORR) and MRD negativity rate at 10-5 sensitivity were included as secondary endpoints.Sanof

An Unexpected Innocent Complication Associated with Azacitidine Treatment of Myelodysplastic Syndrome: Erythema Annulare Centrifugum

Skin lesions accompanying hematological malignancies can be formed due to either direct tumor infiltration of the skin or indirect effects. Indirectly developing lesions may be a component of paraneoplastic syndrome. Erythema annulare centrifugum (EAC) is considered to be a hypersensitivity reaction developed against various antigens associated with infections, drugs, and endocrine diseases. EAC, rarely seen in neoplastic diseases, has been reported in lymphoma, leukemia, histiocytosis, and prostate cancer. Here we report EAC in a patient using a hypomethylating agent, azacitidine. A 69-year-old female patient was admitted to our polyclinic with weakness and ecchymosis in her legs existing for 3 months. She was considered as having refractory anemia with excess blasts-2 according to myelodysplastic syndrome (MDS) classification [1]. Because there was only hyperdiploidy in conventional cytogenetic examination, she was classified in group intermediate-2 of the International Prognostic Scoring System. She had a history of radical mastectomy and adjuvant chemoradiotherapy for breast cancer 3 years ago. She said that variously sized round and oval erythematous, itching, painless lesions had formed in the abdominal region on the 4th day of azacitidine usage (75 mg/m2/day, 7 days, s.c.) (Figure 1 and 2). There were no concomitant complaints or physical examination findings except fatigue. After azacitidine was stopped, a skin biopsy was taken. In the biopsy, mild perivascular inflammatory infiltration accompanying vascular ectasia in the papillary dermis was detected. The possibility of paraneoplastic syndrome was excluded due to the disappearance of all lesions by 1 week after cessation of treatment. During the second course of azacitidine, the lesions reoccurred on the second day. Subsequently to the second course, the patient died of sepsis, which developed after pneumonia

Multipl myelom ile birlikte olan bir akciğer adenokarsinom olgusu

Multipl myelom kemik iliğinde plazma hücrelerinin malign proliferasyonu, serum veya idrarda monoklonal proteinin saptanması, anemi, hiperkalsemi ve litik kemik lezyonları ile karakterize, ikinci en sık rastlanan hematolojik neoplazidir. Multipl myelomseyrinde veya beraberinde ikincil malignite gelişimi, genel populasyona oranla daha sıktır. Literatür taramasında multiple myelom ile akciğer adenokarsinom ile birlikteliğinin nadir olduğu gözlendi. Bu yazıda Multipl myeloma’ya eşlik eden akciğer adenokarsinom olgusu sunulmuştur.Multiple myeloma is the second most frequent hematologic malignancy, characterized by malignant proliferation of plasma cells in bone marrow, presence of monoclonal protein in serum or urine, anemia, hypercalcemia and lytic bone lesions. Development of secondary malignancy in Multiple myeloma is more common than general population. In literaure, coexistence of multiple myeloma with pulmonary adenocarcinoma is rarely reported. Here we present adenocarcinoma coexisting with Multiple myeloma in a case

Nosocomial respiratory syncytial virus infections in three cases in a bone marrow transplantation unit

Bu raporda, hematolojik hastalığı nedeni ile erişkin kan kök hücre nakli (KKHN) ünitesinde yatmakta olan üç hastada solunum sinsityal virus (RSV) enfeksiyonunun yayılımı ve nakil sonrası sonuçlara etkisi sunulmaktadır. Hastalar, hazırlama rejiminin (yüksek doz kemoterapi) uygulanacağı aşamada tek kişilik HEPA filtreli odalarda tersine koruma önlemlerinin alındığı KKHN ünitesine yatırılmıştır. Birinci olgu, yüksek doz steroid içeren rejimlerin olduğu birden çok tedaviye dirençli ilerlemiş multipl miyeloma (MM)'sı olan ve sekonder akut miyeloid lösemi (AML) gelişmiş olan 62 yaşında bir erkek; ikinci olgu ikinci basamak tedavisi ile iyi yanıt elde edildiği halde yüksek doz kemoterapiyi takiben otolog kök hücre infüzyonu yapılan MM'lu 45 yaşında bir erkek; üçüncü olgu ise birden çok tedavi basamağına dirençli kalmış AML tanısı ile akraba dışı vericiden nakil yapılmış olan 52 yaşında bir erkek hastadır. Hastalardan alınan nazofaringeal aspirat sıvısı örneklerinde RSV varlığı, birinci hastada "in-house nested" polimeraz zincir reaksiyonu (PCR) ile, diğer hastalarda ise direk antijen tespiti (Monofluoscreen RSV-Biorad, Fransa) ile araştırılmıştır. Birinci olguda RSV enfeksiyonu kliniği, yüksek doz kemoterapi verildikten sonra KKHN'nin yapıldığı gün ortaya çıkmıştır. RSV-RNA pozitifliğinin saptanması sonucunda oral olarak ribavirin tedavisi başlanmış, engrafman gerçekleşmemiştir. Hastada ciddi solunum yetersizliği ile mekanik ventilasyon ihtiyacı ortaya çıkmış ve olgu kaybedilmiştir. Bu hastada RSV pozitifliğinin saptanması nedeniyle, ünitede yatmakta olan diğer beş hastada haftalık RSV taraması başlatılmıştır. Birinci olguyu takiben sırasıyla dokuz ve 17 gün sonra iki hastada da RSV pozitifliği saptanmıştır. İkinci RSV olgusunda solunum yolu enfeksiyonu kliniği ortaya çıkmış olmasına rağmen üçüncü RSV olgusu asemptomatik kalmıştır. Son iki olguya RSV taramasının ilk pozitif tespitini takiben hemen ribavirin başlanmış ve bu olgularda RSV enfeksiyonu düzelmiştir. Akraba dışı vericiden nakil yapılmış olan üçüncü olguda engrafman gelişmemiş ve ikinci KKHN yapılmıştır. Sonuç olarak KKHN yapılan hastalarda RSV enfeksiyonunun PCR ile erken tanısı, planlanmış immünosüpresif tedavinin ertelenmesi ve tedavi yaklaşımının belirlenmesine fırsat tanıyacaktır.Here we report the spread of respiratory syncytial virus (RSV) infection among three patients, who were hospitalized in an adult hematopoetic stem cell transplantation (HSCT) unit because of hematologic diseases, and effects of RSV infection on post-transplant outcome. The patients were placed into reverse isolation for administration of preparative regimens (high dose chemotherapy) in HSCT unit with high-energy particulate air (HEPA)-filtered single rooms. First case was a 62 years-old man with advanced multiple myeloma, which was refractory to multiple line treatment with high dose steroid including regimens and with secondary acute myelogenous leukaemia (AML); second case was a 45 years-old male patient with multiple myeloma, who had undergone autologous HSCT following high dose chemotherapy; third case was a 52 years-old man with AML that was refractory to multiple line treatment and had undergone allogeneic HSCT from a HLA-matched unrelated donor. Nasopharyngeal aspirate samples were collected from the patients in order to search for RSV positivity. RSV was investigated by in-house nested polymerase chain reaction (PCR) in the first patient and by direct antigen detection method (Monofluoscreen RSV-Biorad, France) in the others. First case had clinical picture of RSV infection just on the HSCT day when high dose chemotherapy has already been given. As RSV-RNA analysis yielded positive result, peroral ribavirin was initiated. Engraftment did not occur in this patient. He developed severe respiratory failure which necessitated mechanical ventilatory support, however, he has succumbed. After the detection of RSV positive index case, weekly screening of RSV in other five patients in the same unit had been performed. Following the first case, after nine and 17 days, respectively, RSV positivity was detected in two more patients. While clinical signs and symptoms of RSV infection developed in second case, third case remained asymptomatic. Both of the following patients had received ribavirin very early at first RSV positivity and recovered from RSV infection. Engraftment did not occur in the last patient who had undergone allogeneic HSCT from a HLA-matched unrelated donor and a second HSCT was performed. As a result, in HSCT patients, early diagnosis of RSV infection by PCR analysis may provide support to postpone immunosupressive treatment and help assesment of the management

Clinical relevance of minor histocompatibility antigens

Conference Conference: 10th Eurasian Hematology Oncology Congress Location: Istanbul, TURKEY Date: OCT 08-11, 2019Objective: The minor histocompatibility antigens (MiHA) are epitopes composed of polymorphic essential peptides evoking alloimmune responses limited to a variety of human leukocyte antigen (HLA) alleles. These peptides are allelic cellular proteins and encoded by autosomal genes or by genes of the Y chromosome. MiHAs may be immunogenic or nonimmunogenic in characteristic. They are either ubiquitously expressed in many cells and tissues or restricted to the hematopoietic system cells. Some of these MiHA can also be expressed by tumor cells. Upon hematopoietic stem cell transplantation (HSCT) for hematological malignancies responses to MiHA may develop as graft-versus-host-disease or graft rejection, but can also contribute to the eradication of the tumor cells named graft-versus.-leukemia effect. Our aim was to determine the MiHA distribution in Turkish healthy population and in patients with hematopoietic malignancies whereas some of them were genotypically identical HSCT recipient/donor pair

Allogeneic hematopoietic stem cell transplantation for adult acute lymphoblastic leukemia: Results from a single center, 1993-2011

Background: For adult ALL patients, the indications and appropriate timing of allogeneic hematopoietic stem cell transplantation (AHSCT) continue to be debated. The primary aim of this single-institution study was to compare the results of our adult ALL patients that had been allografted with those reported in the current literature. Subjects and Methods: This study included 53 consecutive adults with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic stem cell transplantation (AHSCT) with myeloablative (92%) and reduced-intensity (8%) conditioning between 1993 and 2011. Results: Mean patient age was 27 years (SD: 8.62) and donor age was 33.7 years (SD: 9.47). Fourteen patients were in first remission; 21 in ?2nd remission, 15 in relapse and 3 had primary refractory leukemia. Thirty-four, 15 and 4 patients received busulfan plus cyclophosphamide, cyclophosphamide/total body irradiation and fludarabine-based regimens, respectively. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine plus methotrexate were used. Forty-six donors were related and 7 were unrelated. Thirty patients received granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood and 23 received bone marrow as stem cell source. Twenty-six patients relapsed at a mean duration of 11.3 months (SD: 19.1). Forty-four patients succumbed to their disease after a mean follow-up of 13.6 months (SD: 19.5). The cause of mortality was relapse (n=24; 54.5%) and transplant-related etiologies (n=20; 45.5%). The estimated five year probabilities of overall survival (OS) and progression-free survival (PFS) were 37% and 12%, respectively. Conclusion: By multivariate analyses, transplantation in first remission was the most important predictor of transplant success

Infectious epidemiology in multiple myeloma patients after autologous stem cell transplantation: A single-center analysis from Turkey

...European Soc Blood & Marrow Transplanta