Pustular mycosis fungoides has a poor outcome: a multicentric clinico-pathological and molecular case series study.

BACKGROUND: Mycosis fungoides (MF) has usually an indolent course. However, some patients develop a more aggressive disease and few prognostic parameters have been identified. Isolated cases of pustular MF (pMF) suggest an unfavourable prognosis. OBJECTIVES: We aim to describe the clinico-pathological characteristics and prognostic value of pMF. METHODS: We retrospectively collected data of all cases of MF with histological pustules diagnosed from 2009 to 2020. The outcomes and clinico-pathological characteristics of pMF at diagnosis (pMFD) were compared to those of a cohort of non-pustular MF (NpMF). RESULTS: 33 pMF (including 22 pMFD) and 86 NpMF cases were included. The median age at diagnosis of pMF was 61 years [IQR=50-75]. The median follow-up of pMFD was 32 months [IQR=14-49]. Clinically, 33% of pMF had pustules. Large-cell transformation (LCT) occurred in 17 cases. pMFD were at a significantly more advanced-stage and more showed LCT at diagnosis than NpMF (50% vs 7%, p<0.001 and 23% vs 0%, p<0.001, respectively). In multivariate Cox analysis, the presence of histological pustule at diagnostic was associated with shorter OS in all patients (HR=13.90, CI95%[2.43-79]; p=0.003), and in early-stage patients (HR=11.09, CI95%[1.56-78.82]; p=0.02). In multivariate Fine and Gray model analysis, pMFD was associated with a higher cumulative incidence of LCT (SHR=13.90, CI95% [2.43-79]; p=0.003) in all patients. Median OS after the occurrence of histological pustules during follow-up of all pMF patients was 37 months, with a five-year OS of 25% (CI95% [0.06-0.5]). CONCLUSION: pMF often follows an aggressive course, with a high risk of LCT and shorter survival, even for early-stage patients. Histological pustules at diagnostic of MF might represent an independent poor prognostic factor, to be confirmed by further studies. Because pustules are not always clinically identified, histological pustules should be mentioned in pathology reports of MF and prompt discussion of a closer follow-up.

Baseline circulating tumour DNA and total metabolic tumour volume as early outcome predictors in aggressive large B-cell lymphoma. A real-world 112-patient cohort.

Approximately 20%-50% of patients with large B-cell lymphoma (LBCL) experience poor outcomes. We aimed to evaluate the combined prognostic value of circulating tumour DNA (ctDNA) and total metabolic tumour volume (TMTV) in LBCL. This observational single-centre study included 112 newly diagnosed LBCL patients, receiving R-CHOP/R-CHOP-like chemotherapies. CtDNA load was calculated following next-generation sequencing of cell-free DNA (cfDNA) using a targeted 40-gene lymphopanel. TMTV was measured using a fully automated artificial intelligence-based method for lymphoma lesion segmentation. CtDNA was detected in cfDNA samples from 95 patients with a median concentration of 3.15 log haploid genome equivalents per mL. TMTV measurements were available for 102 patients. The median TMTV was 501 mL. High ctDNA load (>3.57 log hGE/mL) or high TMTV (>200 mL) were associated with shorter 1-year PFS (44% vs. 83%, p < 0.001 and 64% vs. 97%, p = 0.002, respectively). When combined, three prognostic groups were identified. The shortest PFS was observed when both TMTV and ctDNA load were high (p < 0.001). Even with a short follow up, combining ctDNA load with TMTV improved the risk stratification of patients with aggressive LBCL. In the near future, very high-risk patients could benefit from CAR T-cell therapy or bispecific antibodies as first-line treatments.

Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab-chemotherapy responsive elderly DLBCL patients: A LYSA group study.

Low baseline NK-cell counts (NKCCs) in patients with diffuse large B-cell lymphoma (DLBCL) are associated with a poor prognosis. The REMARC phase III trial (NCT01122472) showed that lenalidomide maintenance prolonged PFS in rituximab-chemotherapy responders. We conducted a REMARC ancillary study analysing the impact of lenalidomide maintenance on the prognostic value of low NKCCs. Blood samples from 335 elderly French patients enrolled in the REMARC trial were analysed by flow cytometry to obtain NKCCs at diagnosis (n = 220), at randomization (n = 186) and/or six months after randomization (n = 184). Baseline NKCCs < 100 cells/µl were associated with shorter PFS and OS (HRs = [2.2 (1.4, 3.3), p < 0.001] and [2.8 (1.7, 4.5), p < 0.001], respectively), independently of aaIPI. In a competing risk analysis, low NKCCs at baseline were associated with a higher risk of relapse/progression (p = 0.0025), but not of death without progression (p = 0.33). Lenalidomide did not affect the prognosis value of low baseline NKCCs (p  = 0.6349). Similar results were obtained for low NKCCs at randomization. Our results demonstrate that low NKCCs at baseline and post rituximab-chemotherapy are robust prognostic factors in DLBCL and reveal that lenalidomide has no impact on this parameter. Other therapeutic strategies aiming at improving NK-cell function could improve outcomes in DLBCL.