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Background
Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis and lack of adequate therapy options persistently result in permanent impairment of brain functions. Due to profound T cell depletion, impairment of T-cell function and potent immunosuppressive factors, allogeneic hematopoietic cell transplantation recipients are at high risk for JCV reactivation. To date, PML is almost universally fatal when occurring after allo-HCT.
Methods
To optimize therapy specificity, we enriched JCV specific T-cells out of the donor T-cell repertoire from the HLA-identical, anti-JCV-antibody positive family stem cell donor by unstimulated peripheral apheresis [1]. For this, we selected T cells responsive to five JCV peptide libraries via the Cytokine Capture System technology. It enables the enrichment of JCV specific T cells via identification of stimulus-induced interferon gamma secretion.
Results
Despite low frequencies of responsive T cells, we succeeded in generating a product containing 20 000 JCV reactive T cells ready for patient infusion. The adoptive cell transfer was performed without complication. Consequently, the clinical course stabilized and the patient slowly went into remission of PML with JCV negative CSF and containment of PML lesion expansion.
Conclusion
We report for the first time feasibility of generating T cells with possible anti-JCV activity from a seropositive family donor, a variation of virus specific T-cell therapies suitable for the post allo transplant setting. We also present the unusual case for successful treatment of PML after allo-HCT via virus specific T-cell therapy.
Safety and tolerability of SGLT2 inhibitors in cardiac amyloidosis — a clinical feasibility study
(2024)
Sodium-glucose transport protein 2 inhibitors (SGLT2i) slow the progression of renal dysfunction and improve the prognosis of patients with heart failure. Amyloidosis constitutes an important subgroup for which evidence is lacking. Amyloidotic fibrils originating from misfolded transthyretin and light chains are the causal agents in ATTR and AL amyloidosis. In these most frequent subtypes, cardiac involvement is the most common organ manifestation. Because cardiac and renal function frequently deteriorate over time, even under best available treatment, SGLT2i emerge as a promising treatment option due to their reno- and cardioprotective properties. We retrospectively analyzed patients with cardiac amyloidosis, who received either dapagliflozin or empagliflozin. Out of 79 patients, 5.1% had urinary tract infections; 2 stopped SGLT2i therapy; and 2.5% died unrelated to the intake of SGLT2i. No genital mycotic infections were observed. As expected, a slight drop in the glomerular filtration rate was noted, while the NYHA functional status, cardiac and hepatic function, as well as the 6 min walk distance remained stable over time. These data provide a rationale for the use of SGLT2i in patients with amyloidosis and concomitant cardiac or renal dysfunction. Prospective randomized data are desired to confirm safety and to prove efficacy in this increasingly important group of patients.
Background
Even in the era of novel immunotherapies for multiple myeloma (MM), treatment of late‐stage relapsed/refractory (RR) patients remains challenging. The aim of our study was to analyze the efficacy and safety of the five‐drug combination pomalidomide, bortezomib, doxorubicin, dexamethasone, and daratumumab (“Pom‐PAD‐Dara”) in RRMM.
Methods
We retrospectively analyzed data of 56 patients with RRMM who received Pom‐PAD‐Dara between September 2016 and May 2019.
Results
Patients were heavily pretreated with a median of four prior lines of therapy, including autologous and allogenic stem cell transplant in 50 (89%) and six (11%) patients, respectively. The overall response rate (ORR) was 78% and we observed partial remission, very good partial remission, and complete remission in 27 (48%), 13 (23%) and four (7%) patients, respectively. Median progression‐free survival was 7 months (95% CI, 3.3‐10.7) and the median overall survival was not reached at 24 months. Adverse events grade ≥ 3 were observed 41 (73%) patients and included neutropenia (n = 28, 50%), anemia (n = 22, 39%), thrombocytopenia (n = 21, 38%), and pneumonia (n = 6, 11%).
Conclusion
Pom‐PAD‐Dara represents a promising multiagent regimen in heavily pretreated RRMM patients with high ORR and an acceptable safety profile.