Page 285 - 2021_02-Haematologica-web

Letters to the Editor
imab were not associated with OS (Online Supplementary Table S2). Excluding the four patients in the chemothera- py group who subsequently received whole-brain radio- therapy did not change survival estimates. Within the chemotherapy group, median OS for recipients of MTX- monotherapy was 5 months (95%CI: 2.6-41.4) and for MTX-based regimens 27 months (95%CI: 10.3-not reached) (Figure 1D) but was was not statistically signifi- cant (P=0.170). Also, and more importantly, the number of patients was too small to allow a meaningful compar- ison to be made. Therefore, a multivariable analysis of MTX only versus MTX-based regimens was not per- formed.
In this contemporary, nationwide, population-based study among newly diagnosed PCNSL patients >70 years old we observed that the prognosis of these patients remains poor. This finding agrees with prior population- based studies spanning the past decades.1
Age is a strong prognostic factor in adult PCNSL patients.9,10 However, within our study population of patients >70 years old, there was no clear prognostic gra- dient with increasing age, although with larger patient numbers, a statistically significant association between age and OS might be seen. Instead, despite the small patient numbers, treatment was a strong prognostic fac- tor. Although only 22% of patients aged ≥80 years received chemotherapy (which possibly hints towards selection bias or confounding by indication) this finding suggests that treatment, more than age, influences sur- vival in elderly patients judged fit enough to receive ther- apy. Selection bias might also have impacted MTX- monotherapy versus MTX-based chemotherapy; perform- ance status and comorbidity, in particular renal insuffi- ciency, might have influenced the choice of chemothera- peutic regimen.
Prior prospective studies provided evidence that high- dose MTX, especially when combined with alkylating chemotherapy, is the most efficacious treatment for eld- erly PCNSL patients.11 Although there are conflicting data
on the therapeutic value of chemoradiation over chemotherapy alone in elderly PCNSL patients,11,12 it is unquestionable that consolidation with radiotherapy in this population carries a high risk of neurotoxicity and severe cognitive decline.13
Controversy remains regarding the therapeutic value of rituximab in PCNSL. Findings from the current study and a recent randomized phase III trial among PCNSL patients aged 18-70 years showed no added therapeutic value of rituximab on survival outcomes.3 However, our results should be interpreted with caution given the low number of rituximab-treated patients. Similarly, a meta- analysis of 343 patients with PCNSL aged 50-67 years showed a possible positive effect of rituximab on PFS but not on OS.14 In contrast, a recent population-based study among 164 adult PCNSL patients diagnosed between 2005-2010 in Austria, of whom 40% were >70 years old, after a short follow-up (median 12 months) suggested that rituximab might increase survival.15
The strength of the current study is the use of a nation- wide population-based cancer registry. As such, our find- ings are not compromised by selection and/or referral biases to the extent encountered in clinical trials. Therefore, our study represents the general population of elderly PCNSL patients. Limitations of our study mainly concern the lack of data throughout most of the registry on comorbidities, the use of corticosteroids, and the dose of steroids and chemotherapeutic agents, relapse rates, and salvage treatment. In addition, the performance score is poorly documented in medical records, thereby hampering its inclusion in the regression analyses due to the high percentage of unknown values (48%) (Table 1); this limits its contribution to the clinical decision-making process based on performance status.
In summary, in this nationwide, population-based study, survival among PCNSL patients >70 years old remains poor in contemporary clinical practice. Nevertheless, our data demonstrate that MTX-based multi-agent chemotherapy, as compared with radiothera-
Table 2. Detailed information on primary therapy in over 70-year old patients with PCNSL. Age at diagnosis, years
≥80
Total
Primary therapy N
Total n. of patients 55 Supportive care only 17 Radiotherapy alone 6 Chemotherapy 32
(%) N
(%) N
32 (38) 15 (22) 10
(40) 7 (26) 1 (17) 0 (5) 1 (2) 0
(%) N
145 (47) 54 (31) 29 (22) 62 (3) 36 - 25
(3) 6 -2 -1 -1 -1
(%)
(37) (20) (43) (25) (17) (4) (1) (1) (1) (1) (17) (1) (1)
71-74
75-79
58 (31) 22 (11) 13 (58) 23 (36) 15 (27) 10
MTX-based 20
MBVPa,e 15
MPb,f 2 (4) 3 MCPMc 1 (2) 1 MCPc 1 (2) 0 R-CHOP + MTX 0-1 MAc 1 (2) 0
- 0 (2) 0 - 0
MTX onlyd 12 (22) 7 Other 0 - 1 PC 0 - 1
(12)
(2)
(2)
6 (19) 25
0 - 1
0 - 1
MTX:methotrexate;MBVP: MTX,teniposide,carmustine,andprednisolone;MP: methotrexateandprocarbazine;MCPM: methotrexate,lomustine,procarbazine,andcytara- bine;MCP:methotrexate,lomustine,andprocarbazine;R-CHOP:rituximab,cyclophosphamide,doxorubicin,vincristine,andprednisone;MA:MTXandcytarabine;PC: pro- carbazine and lomustine. aCytarabine and rituximab were applied in 15 and 2 patients, respectively. bRituximab was applied in 5 patients. cRituximab was applied in 1 patient. dRituximab was applied in 6 patients. eWhole brain radiotherapy was administered after chemotherapy in 3 patients. fWhole brain radiotherapy was administered after chemotherapy in 1 patient.
haematologica | 2021; 106(2)
599