Relationship Between Socioeconomic Factors and Delay in Diagnosis and Initial Treatment in Patients With Difusse Large B Cell Lymphoma (Dlbcl). Do These Factors Impact on the Response Rate? Results of a Multicentric Argentinian Study

Introduction: Immunochemotherapy (ICT) with R-CHOP (or R-CHOP-like) is the standard of care for patients (pts) diagnosed with DLBCL. Due to the aggressiveness of these lymphomas and their potential curability treated with the standard of care, treatment should be initiated without delay. Objectives: To define the impact generated by the delay in the different diagnostic-therapeutic stages, from the onset of symptoms to the administration of ICT, on therapeutic response rates in a series of pts diagnosed with DLBCL from various institutions from Argentina (public and private). We focused our analysis on the reasons of delay and their relationship with socioeconomic factors. Patients and methods: We designed a multicentric, descriptive, retrospective study in which patients diagnosed with DLBCL between 2/2004 and 4/2015 in the participating institutions were registered. Variables of interest were: date of beginning of the symptoms, 1st consultation, date of anatomopathological diagnosis, beginning and end of treatment. All causes of identified delay on the process of diagnosis and treatment were recorded. The place of residence, educational level, health care coverage, availability of rituximab (R) in 1st cycle and response rate, completed the studied variables. Results: 278 pts were recorded (Male/female ratio: 1.007/1). Median age was 54 years old (19-88 years). The interval between symptoms onset and 1st consultation was variable (258 pts): <3 months: 65.11%; 3-6 months: 24.03%; 6-12 months: 7.36%, and more 1 year: 3.48%. The delay was not related to social coverage or educational level, but related to psychological factors: reluctance to consultation in the majority of pts (probably negation). Clinical presentation: ECOG PS: 75% of pts had scores 0-1, only 3% had ECOG:4. 49% of pts had advanced disease (Ann-Arbor III-IV); 18.54% were stage I. Bulky disease was present in 21.08%, and 46% of pts had B symptoms. Extranodal (EN) compromise was present in 55.3% (141/255pts: EN 1: 87.23%; EN 2: 11.34%; EN 3: 1.41%). LDH was increased in the half of pts. Distribution by IPI score was: low: (0-1): 49.09%, Int/low (2): 25.45%, Int/high (3): 16.72% and High (4-5): 8.72%. 55.09 % of pts had social security, 21.50% private medicine and 23.39% had public health system assistance. 12.33% of pts came from rural areas and 11.03% were foreigners (neighbor countries). The 26.25% had university education, 36.25% completed high-school, 36.87% primary and 0.62% were illiterate. The interval between diagnosis and onset of ICT (data from 252 pts) was 1 month in 37.3%; 1-3 months: 21.82% and,≥ 4 months: 5.55% of pts (delay was due to staging process and variable access to ICT). There were no delays in the availability of chemotherapy drugs, but the 27.34% (73/267) did not receive R in 1st cycle due to lack of access. 10.11% received R for advancement from the institution. Only in 62% of pts (167/267) R was available from the 1st cycle by the health coverage. The response rate among the 250 pts treated and evaluable was: 75.60% CR, 12.40% PR, 1.60 % SD and 10.40% PD. Surprisingly there was no correlation between CR rate and delay to the 1st consultation (p=0.31), as well as CR rate and the interval between diagnosis and time to ICT onset (probably due to the low number of cases). Not receiving R from the 1st cycle of ICT was inversely correlated to CR rate (p=0.0063), although these patients completed all doses of rituximab. Discussion: Argentina has a very heterogeneous health system (public, social security and prepaid medicine). The availability of chemotherapeutic drugs is guaranteed by law, but there are differences and delays in the access to high-cost drugs, depending on the payers. Our patients population receive attention in public and private hospitals with different funding sources and access to high cost medication, such as monoclonal antibodies. To emphasize this aspect, our results show that the only variable with impact in the response rate was the fact of not receiving R from the 1st treatment cycle. Conclusion: A prompt beginning ofICT is essential to obtain CR in pts diagnosed with DLBCL. An unacceptable proportion of our DLBCL pts (30%) receive the ICT with some degree of delay, which decreases their chances of achieving CR.