7.3. Role of transplant

7. Treatment

Treatment for DLBCL includes chemo-immunotherapy with an anthracycline backbone.

Limited stage DLBCL which is usually Ann Arbor stage I or II ( usually non-bulky stage II which may be included in one irradiation field) accounts for 30-40% of patients with DLBCL. Combined modality therapy is considered the standard of care for these patients. This was initially established by a large randomized SWOG 8736 trial which was conducted in the prerituximab era. The trial compared 3 cycles of CHOP plus RT (radiotherapy) vs. 8 cycles of CHOP alone in localized stage IE, non-bulky stage IIE aggressive lymphoma. The PFS for patients receiving CHOP plus RT and for patients receiving CHOP alone were 77 and 64%, p = 0.03, respectively. The 5 year OS for patients receiving CHOP plus RT vs. CHOP alone were 82 and 72%, p = 0.02, respectively [61]. However, further follow up showed that the advantage negated. Patients with RT had more late relapses while patients with CHOP alone had increased toxicity. Addition of rituximab to combination chemo showed improved responses in patients with early stage disease. In a multicenter randomized clinical trial, MInT, which comprised of atleast 2/3rd early stage patients, 3-year event-free survival (EFS) in R-Chemo arm (79% [95% CI 75–83]) was higher as compared to chemo alone arm (59% [54–64]) and 3 year overall survival (OS) in R-chemo arm was also higher than the chemo alone arm (93 vs. 84%) [62]. The SWOG S0014 study [63] was a phase II study where patients with limited stage disease and at least 1 adverse feature, based on stage modified-IPI were given rituximab with 3 cycles of CHOP followed by involved field radiation therapy (IFRT). The study showed 2-year PFS of 93% and 4 years PFS of 88%. OS was 95% at 2 years and 93% at 4 years. These results were better than SWOG 8736 trial where CHOP+ RT without rituximab was given. R-CHOP 3 followed by RT remains the standard of care for patients with limited stage non-bulky disease while R-CHOP 6 cycles with or without RT remains the standard for patients with

60–70% of patients present with advanced disease. R-CHOP every 21 days is the standard of care for this group of patients. About 60% of patients are cured with this approach. The beginnings of modern chemotherapy dates back to the use of nitrogen mustard with remarkable tumor response in a patient at Yale in 1942. The initial use of Adriamycin containing drug combinations (CHOP) was reported in 1979 by Miller et al. in 45 patients with localized NHL [61]. In Phase III trials, a complete remission (CR) rate was 53% and the survival rate was 30% after 12 years of follow up [64]. Several intense regimens such as m-BACOD; proMACe-CytaBOM and MACOP-B were investigated to improve on the results of CHOP. SWOG and ECOG did a prospective randomized phase III trial to compare these with CHOP and found no difference between these regimens but higher toxicity with the intense regimens [65]. It

Options differ for patients with limited vs. advanced disease.

7.1. Initial treatment of limited stage DLBCL

54 Hematology - Latest Research and Clinical Advances

limited stage bulky disease (NCCN guidelines).

7.2. Initial treatment of advanced stage DLBCL

High-dose therapy with autologous stem cell rescue (HDT/ASCR) has shown significant improvement in OS and PFS in pre-rituximab era [69, 70]. However in the era of chemoimmunotherapy with addition of rituximab to chemotherapy, the indication for HDT/ASCR has significantly become limited with many studies showing no statistical significant advantage of proceeding to transplant in first remission except may be in patients with high risk score [71, 72].
