Page 179 - Haematologica Vol. 107 - September 2022

ARTICLE - Rituximab with LMB-chemotherapy regimen in PMLBL M.E. Dourthe et al. Figure 3. Events.
Patient identification number
First line therapy
Site of progression/ relapse
Time from inclusion
2nd line chemo- therapy
Radiation therapy
High dose chemo- therapy
Patient status at last news
PMLBL1
Group B, R-
mediastinum
Progression after CYVE1 3.4 months*
R-DHAP (3): progression R-ICE (2):
progression
No
No
DOD, 23 months
PMLBL2
Group B, R-
mediastinum
Progression after CYM 3.5 months1
R-ICE (2): progression
R-EPOCH (2): progression
No
No
DOD, 9.3 months
PMLBL3
Group B, R-
mediastinum
Viable cells
in residual mass after CYVE2 5.2 months
R-ICE (2)
Yes
BEAM and ASCT
CR, 6.9 years
PMLBL4
Group B, R-
mediastinum
Local relapse 9.9 months
CYVE (2) R (4)
No
No
CR2, 6.7 years
PMLBL5
Group B switched to C after COP, R+
mediastinum
Progression after R-COPADM1 0.6 months
R-ICE (3)
Yes
BEAM and ASCT
CR, 11 years
R: rituximab; BEAM: carmustine, etoposide, cytarabine, melphalan; DHAP: dexamethasone, high dose aracytin, cisplatinum; ICE: ifosfamide, etoposide, carboplatin; EPOCH: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin; ASCT: autologous stem cell transplantation; CR: complete remission; DOD: died of disease. *Candidemia after prolonged aplasia followed by disease progression.
Histological characteristics
The national pathological review was done for 36 of 42 pa- tients (86%) and PMLBL diagnosis was confirmed for all except one case. For one case, a consensus diagnosis was not reached (differential diagnosis between PMLBL and grey zone lymphoma). The remaining six patients had a local pathological report compatible with the diagnosis of PMLBL.
All cases expressed B-cell marker CD20 and were negative for CD3. CD10, BCL6, MUM1, BCL2, CD23 expression were evaluated for 12 cases and showed staining in 21%, 73%, 55%, 42%, and 46% of cases, respectively. CD30 staining was weak and patchy found in 66% of cases. PDL1 ex- pression was observed on tumor cells in 85% of cases. Fi- nally, only one of 23 cases tested had EBER positivity by in situ hybridization.
Treatment and response
All patients received LMB-based chemotherapy: 19 pa- tients were treated in Group B, 18 in Group C, and five with LMB-modified B/C. Twenty-one patients received rituxi- mab (R+) (after 2008) while 21 did not (R-). Of the 40 (95%) patients who were received COP therapy, 33 had at least a 20% response. Two patients were transferred to Group C after COP therapy (1 R- ; 1 R+). Three patients had dis- ease progression during therapy (2 R-, 1 R+). Among the
39 other patients, at remission assessment, two patients were in complete response (CR) while 37 had a residual mass on imaging, with a median size of 50 mm (range, 17- 135; data available for 30 patients). In total, 26 of 37 had biopsies, excisions or partial excisions: one had viable tumor cells (R-; tumor size: 68 mm after CYM1 vs. 108 mm at baseline) and for all other patients, the histology re- vealed complete necrosis. Thirty-eight patients (90%, 95% CI: 77-97) were considered to have achieved CR (2 CR, 25 complete necrosis, and 11 residual mass not explored). Thirty-seven patients (88%) had 18F-FDG PET/CT at re- mission assessment after a median of four chemotherapy courses (range, 3-6) of whom 26 (70%) were considered positive according to current Cheson criteria.15 Among these 26 patients, four had further treatment failure, in- cluding one with histology positive residual disease, one with complete necrosis on biopsy, and two not biopsied (predictive positive value =15%; 95% CI: 4-35). Among the 11 patients with negative 18F-FDG PET/CT, none had treat- ment failure (predictive negative value =100%; 95% CI: 72- 100).
Outcome
The median follow-up was 7.1 years (interquartile range, 5.8-11.1), 10.6 years for patients treated without rituximab, and 6.4 years for patients treated with rituximab. There
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