Switching between different therapeutic FVIII concentrate types has been postulated as a possible cause of inhibitor development in patient with haemophilia A. In this single-centre, retrospective study, the incidence, titre and duration of inhibitor development in multitransfused patients, defined as patients with more than 150 exposure days (ED), were analysed from January 1970 to December 2007 in relation to ED and the number of switches between different products. Inhibitor titre was assessed by Bethesda assay (before 1998) or Nijmegen assay (after 1998). Medical records of 167 patients were screened, of which 97 patients met the inclusion criteria. Fourteen products of plasmatic origin (different purities) and five recombinant (three generations) were used. Nine patients (9%) developed inhibitors, all transient, low-titre (1.41 ± 0.54 BU) after 323 ± 287 ED in average. Seventeen patients had no product switches of which four patients (23%) developed inhibitors (97 ED in average), whereas 13 patients (77%) did not (ED: 230). Fifty patients switched between plasmatic products only (median: 10 changes) of which five patients (10%) developed inhibitors (ED: 503), whereas 45 patients did not (ED: 932). Five patients switched between recombinant products only (seven changes) of which no patient developed inhibitors (748 ED). Twenty-five patients switched between plasmatic and recombinant products (13 changes) of which no patient developed inhibitors (ED: 1654). No statistically significant differences between patient groups were observed. Neither the number of different FVIII products administered nor the switching of products influenced the incidence of inhibitor in multitransfused patients.

Background: Heavily pretreated relapsed and refractory multiple myeloma (RR MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short (Richardson et al. 2007). Belantamab Mafodotin (BM), a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin F, showed single-agent activity in the phase 1 DREAMM-1 and phase 2 DREAMM-2 studies in heavily pre-treated patients with RRMM (Lonial et al, 2019 & 2021). We aim to assess efficacy and safety of BM treatment administered via the expanded access compassionate care program for triple class MMRR patients in the region of Madrid (Spain). Methods: An observational, retrospective and multicenter study has been performed including all patients who received at least one dose of BM under the expanded access program in the region of Madrid (Spain) from Nov 2019 to Jun 2021. Hematology centers provided data from the medical records and entered them in a case report form distributed to the sites. Primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and the incidence of treatment emergent adverse events (TEAEs), with a major focus on ocular and hematologic toxicity. Results: A total of 33 patients (pts), from 14 different centers, were included from February 2020 till May 2021. Median age was 70 (46-79) years. 55% of the pts were women. Median time from diagnosis was 71 (10-858) months. 30.3% were high-risk cytogenetic features. Median of prior therapy lines was 5 (3-8) and at least 88% of the pts were triple class refractory. The median number of BM doses per patient was 3 (1-16) and the median follow-up was 11 months (95%CI 6.34-15.66). ORR was 42.2%, and 18.2% achieved ≥VGPR. Median PFS was 3 months (95%CI 0.92-5.08). Median PFS for patients who achieved ≥PR was 11 months (HR 0,26; 95% CI 0,10-0,68). No significant differences were found in PFS according to age, cytogenetic risk and prior therapy lines. OS was 424 days (95% CI 107-740). The incidence of non-hematological TEAEs was 57.6% and the most common of which was ocular toxicity (45.5%). The incidence of ≥G3 non-hematological TEAEs was 30.3%. 51.5% of the pts were diagnosed of keratopathy and 21.2% was ≥G3. 30.3% of the pts showed a reduced visual acuity, but this event was resolved in 92.9% of the pts. The most common symptoms were blurry vision (30.3%, n=10) and dry eye (24.2%, n=8). The incidence of ≥G3 hematological TEAEs was 18.2% and thrombocytopenia was the most frequent (21.2%). Dose reductions of BM were required in 30.3% of the pts and delayed in 36.4% due to TEAEs. Main causes for treatment discontinuation (81%, n=27) were disease progression (54.5%, n=18), toxicity (15.2%, n=5), death (6.1%, n=3) and due to patient's decision (3%, n=1). Conclusion: Compassionate use of BM in heavily pretreated RR MM pts showed a relevant anti-myeloma activity with a manageable safety profile.These results are similar to those observed in the DREAMM-1 and DREAMM-2 clinical trials. Disclosures No relevant conflicts of interest to declare.

Acute myeloid leukemia (AML) is the most common acute leukemia in the adult population and largely affects older patients with a median age at diagnosis of 68 years. 1 Elderly patients with AML often respond poorly to induction chemotherapy as a result of higher frequency of adverse genome features and increased resistance to treatment. 2,3 Furthermore, because of comorbidities, compromised organ function, and poor performance status, older patients may not be candidates for conventional cytotoxic induction therapies, 2,4-6 and therefore, treatment options for unfit patients have historically been limited. 7 Less intensive approaches to treatment, such as low-dose cytarabine (LDAC), have shown poor response rates (11%-19%) and short median survival rates (<6 months). 8,9 Similarly, hypomethylating agents (HMA) azacitidine and decitabine in monotherapy are associated with a tolerable safety profile, complete remission (CR) plus CR with incomplete count recovery (CRi) rates of 15%-30%, and median overall survival (OS) of <12 months. 10,11 In November 2018, the Food and Drug Administration (FDA) approved the selective BCL-2 inhibitor venetoclax in combination with either HMA or LDAC in older or unfit patients with AML. 7 Venetoclax has shown encouraging activity when combined with HMA agents. 2,12 Venetoclax 400 mg plus HMA (Ven/HMA) in newly diagnosed AML patients without prior HMA exposure led to a 73% rate of CR + CRi, 2 while, in relapsed/refractory (r/r) AML patients (61% with prior HMA failure), it was observed with an ORR (CR + CRi) of 51%. 12 The combination is well-tolerated even in fragile

A middle-aged female arrived at a tertiary care hospital after a referral from her primary care physician to evaluate a left breast mass found on ultrasound concerning malignancy. The patient was also 27 weeks gestational with monochorionic diamniotic twins. During triage, she was found to have severe hypertension and lab abnormalities concerning HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome and underwent cesarean delivery of the infants. She had a biopsy of the left breast mass post-delivery, later diagnosed as invasive ductal cell carcinoma with spinal metastasis and numerous metastatic pulmonary nodules. Her hospital stay was complicated by a right lower extremity deep vein thrombosis, acute subdural hematoma, and disseminated intravascular coagulation with refractory thrombocytopenia resulting in her death.

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