[Five year experience in ibrutinib therapy for relapsed and refractory mantle cell lymphoma in real world Russian clinical practice].

BACKGROUND: Mantle cell lymphoma (MCL) is a rare and clinically aggressive lymphoma subtype. Current approaches have greatly improved patients outcomes, but relapse is inevitable. In phase IIIII clinical trials, ibrutinib has shown significant activity in patients with relapsed or refractory (R/R) MCL. AIM: To assess efficacy and toxicity of ibrutinib monotherapy in patients with R/R MCL in routine practice outside of clinical trials. MATERIALS AND METHODS: The study enrolled patients with confirmed R/R MCL who had received at least one line of previous chemotherapy. ECOG 24, cytopenia, infectious complications, hemorrhagic syndrome were not exclusion criteria. Patients received daily oral ibrutinib 560 mg until progression or unacceptable toxicity. RESULTS: From May 2015 to September 2020 ibrutinib therapy was started in 106 patients with R/R MCL in 16 regions of Russia. The median age was 66 years; ECOG2 18%, blastoid variant (or Ki6740% or WBC50109/l) 43%. The median number of previous treatment lines was 2 (111). The ORR was 78.4% (CRR 27.4%). The median PFS was 13.6 months and OS 23.2 months. In the blastoid group the median PFS was 4.4 months vs 36.5 months in the alternative group (p0.001), the median OS 9.0 vs 41.0 (p=0.001). The median OS of patients after progression on ibrutinib was 3.2 months. The common complications are hemorrhages (63%), diarrhea (62%), myalgia and muscle cramps (60%), infections (31%), skin and nail toxicity 15%, arrhythmia 8%. None of recipients had to completely discontinue ibrutinib therapy due to complications. CONCLUSION: Ibrutinib is effective and well tolerated in routine practice of R/R MCL treatment and our results are consistent with international clinical trials. The favorable toxicity profile and the high response rate made it possible to prescribe ibrutinib in severe somatic status, cytopenia, and even in the presence of infectious complications.

[The effect of polymorphisms C677T and 1298 gene MTHFR on the reproductive function of men].

References. Disturbances of spermogram parameters are associated with infertility in men and are determined by polymorphisms of many genes involved in spermatogenesis. Folate metabolism plays an important role in spermatogenesis, as it is involved in the synthesis, repair and methylation of DNA. OBJECTIVE: the distribution of C677T (rs1801133) and A1298C (rs1801131) polymorphisms of the MTHFR gene among infertile and fertile men in the Moscow region and to identify a possible Association of these polymorphisms with the risk of pathospermia. MATERIALS AND METHODS: the study included 127 infertile men with different forms of pathospermia and 68 fertile men (with one or more children). Genotyping of polymorphisms (C677T and A1298C) gene MTHFR was performed by real-time polymerase chain reaction (PCR-RV). RESULTS: Analysis of the distribution of MTHFR genotypes (C677T and A1298C) revealed no significant differences in the distribution of genotypes in groups of infertile and fertile men. The frequency of minor allele 1298S in asthenospermia was 52%, in teratospermia was 36% and in men with azzospermia - 33% (2=8.67; p=0.003). DISCUSSION: To date, there are no published results on the study of the Association of polymorphisms of folate-metabolizing enzyme genes with the development of pathospermia among men in the Moscow region. The results of our study demonstrate that 1298 polymorphism of the MTHFR gene may be involved in the etiology of male infertility in patients of the Moscow region. CONCLUSION: Comparative analysis of gene and genotype frequencies by the studied polymorphisms in infertile men with different forms of pathospermia showed an associative relationship of allele 1298C of MTHFR gene with the risk of asthenozoospermia (p<0.05).