Case Report: Avelumab and ruxolitinib to manage polycythemia vera and secondary metastatic Merkel cell carcinoma: a possible successful combination.

We describe a case of second primary malignancy in a 65-year-old patient affected by polycythemia vera treated with the JAK 1/2 inhibitor ruxolitinib. The latter is recognized as a risk factor for the onset of non-melanoma skin cancers in many retrospective and perspective studies, but the concomitant use of ruxolitinib with new immunotherapies is very rarely reported, and the safety of this association is still not clear. In our case, ruxolitinib combined with the anti-PD-L1 avelumab demonstrated both safety and efficacy for hematological disease control and underlying carcinoma remission.

Systemic mastocytosis: 2023 update on diagnosis and management in adults.

INTRODUCTION: Systemic mastocytosis (SM) is a complex and heterogeneous disease, characterized by the clonal accumulation of mast cells in one or more organs. In 2022 both the World Health Organization (WHO) and the International Consensus Classification (ICC) modified the diagnostic and classification criteria of SM. Moreover, the identification of new clinical and molecular variables has improved prognostic tools and led to increasingly individualized therapeutic strategies. AREAS COVERED: The aim of this review is to present the updates introduced by the International Consensus Classification in diagnostic criteria of SM. In addition, we report the latest data available from the most important clinical trials in patients both with non-advanced and advanced disease, including elenestinib and bezuclastinib. EXPERT OPINION: Diagnosis and classification of SM has evolved over years. The most recent WHO and ICC classification improved SM diagnostic work-up, providing clinicians with a clear and simplified diagnostic scheme. New approved targeted therapies such as midostaurin and avapritinib modified the treatment paradigm in patients in advanced stage, and next-generation inhibitors actually investigated in clinical trials are expected in the next future.

Impact of anti-SARS-CoV-2 monoclonal antibodies in the management of patients with lymphoma and COVID19: A retrospective study.

COVID19 in patients affected by lymphoma represents an important challenge because of the higher mortality rate. Anti-SARS-CoV-2 monoclonal antibodies (anti-S MoAbs) appear promising in this setting. We report a monocentric retrospective study including 176 patients affected by lymphoma which developed SARS-CoV-2 infection since the start of COVID19 pandemic. Overall, mortality was 13.1%, with a decreasing trend between first waves to the last wave of pandemic (18.5% vs. 9.4%, p 0.076). Patients receiving anti-S MoAbs (41.3%) showed inferior mortality rate (overall survival, OS 93.2% vs. 82.7%, p 0.025) with no serious toxicity, reduced documented pneumonia (26% vs. 33%, p 0.005), and reduced need of oxygen support (14.5% vs. 35.7%, p 0.003). Among patients who received 3 doses of vaccine, the employment of anti-COVID MoAbs showed a trend of superior survival versus those who did not receive Anti-S MoAbs (OS rates 97.3% vs. 84.2%, p 0.064). On multivariate analysis, active haematological disease (OS 72% (HR 2.49 CI 1.00-6.41), bendamustine exposure (OS 60% HR 4.2 CI 1.69-10.45) and at least one comorbidity (HR 6.53 CI 1.88-22.60) were independent prognostic factors for death. Our study confirms the adverse prognostic role of COVID-19 in lymphoma patients in presence of active disease, comorbidities and previous exposure to bendamustine. In our experience, anti-S MoAbs represented a therapeutic option in vaccinated patients.

Emerging concepts for assessing and predicting treatment-free remission in chronic myeloid leukemia patients.

INTRODUCTION: In chronic myeloid leukemia (CML) patients who have reached a deep and sustained reduction of residual disease can attempt a discontinuation. The 'treatment-free remission' (TFR) has become a real long-term endpoint for 30-40% of chronic phase patients. AREAS COVERED: In this review, we focus our attention on possible prognostic features who can predict the success of tyrosine kinase inhibitors discontinuation and how we can assess the minimal residual disease (MRD) during the TFR phase. Broad research was made on Medline, Embase and archives from EHA and ASH congresses. EXPERT OPINION: Median duration of TKI therapy and of deep molecular response are the main prognostic factors identified in most trials and real-life experiences on discontinuation. Immunological pathways have been proposed as possible control on successful TFR as also early molecular response dynamics. Appropriate molecular monitoring by RQ-PCR in the TFR phase has been proposed by several international recommendations and digital droplet PCR (ddPCR) seems to have a possible role in the future for a better identification of candidate to this possible therapeutic strategy.

Early response to caplacizumab and rituximab after anaphylaxis to Octaplas plasma in a patient with thrombotic thrombocytopenic purpura.

Management of aTTP in patients who refuse or are intolerant to plasma remains challenging, but new drugs can be implemented with success. A 39-year-old woman presented to the Emergency department for bruises at the upper and lower limbs together with worsening anemia and thrombocytopenia; PLASMIC score was seven, indicative of high risk to have a thrombotic microangiopathy due to severe ADAMTS-13 deficiency: indeed, it was 1.4%. We immediately started Plasma Exchange, but after the third procedure she developed severe anaphylaxis to Octaplas plasma, so PEXs were discontinued. We proceeded to a salvage strategy with rituximab and caplacizumab that was rapidly effective to resolve symptoms and hemolysis. It has been already reported a case in which a patient developed severe reactions to fresh-frozen plasma that required discontinuation of PEX. Differently from this case, our patient was already using the less immunogenic pooled plasma units Octaplas, therefore a strategy with caplacizumab was the only available option. Moreover, rituximab is associated with a shorter time to obtain a durable remission in aTTP and a faster time (15 days) to final ADAMTS13 activity recovery >10%. To our knowledge, this is the first case of early discontinuation of caplacizumab in a patient allergic to PEX by actively monitoring ADAMTS13 activity, allowing optimization of healthcare resources during COVID-19 pandemic.

Acute Promyelocytic Leukemia After Radium-223 Exposure for Prostate Cancer in a Chemotherapy-Naïve Patient.

223Ra-dichloride is a bone-seeking targeted alpha (α)-emitting approved for bone metastases in prostate cancer. Here, we report a case of therapy-related acute promyelocytic leukemia (t-APL) following administration of 223Ra, showing some evidence of a causative relationship. A patient with metastatic prostate cancer received therapy with 223Ra, with 6 injections of the radiopharmaceutical at a standard dose of 55 kBq/kg at 4-week intervals for a cumulative administered activity of 26.3 MBq. PET/CT with 18F-methylcholine repeated 1 month after the conclusion of 223Ra was negative. After 8 months, he developed pancytopenia and we made a diagnosis of therapy-related acute promyelocytic leukemia (t-APL). We then studied the genomic locations of the breakpoints in the PML and RARA genes, which were at nucleotide positions 1708-09 of PML intron 3, respectively, outside the previously reported Topo II-associated hotspot region. t-APL was cured with all-trans-retinoic acid (ATRA) and arsenic trioxide. The type of PML/RARA rearrangement we identified, in absence of other myelotoxic treatments, is suggestive of a possible direct causal relationship with exposure to 223Ra and warrants further investigations.