Non Double-Hit Diffuse Large B Cell Lymphoma Treated with R-CHOP Has Excellent Overall Survival If Interim Scan Shows Partial or Complete Response

R-CHOP chemoimmunotherapy is first line therapy for diffuse large B cell non Hodgkin lymphoma (DLBCL), although R-CHOP may be suboptimal treatment for some subtypes of DLBCL, in particular double-hit (DH) or triple-hit (TH) lymphoma. For assessment of response to chemoimmunotherapy, it has been proposed that PET-CT scan may be superior to CT scan and, in particular, demonstration of metabolic complete response (CR) by PET-CT scan at end of treatment (EOT) may be an important indicator of long term survival. However, the usefulness of follow up scans in asymptomatic patients remains debatable.

We wished to assess the role of an interim CT or PET-CT scan (after 3-4 courses of chemoimmunotherapy) in predicting overall survival in patients at our centre with stage II- IV DLCBCL (Lugano Modification of Ann Arbor Classification) who received chemoimmunotherapy with curative intent. We also recorded results of scans at EOT and any further follow up scans.

Between 1/7/15 and 1/7/19, 43 consecutive patients receiving R-CHOP had an interim CT or PET-CT scan. 3 of 4 patients with DH lymphoma by FISH testing changed to dose adjusted R-EPOCH after one course of R-CHOP. 39 patients had no evidence of DH, with 37 showing either partial response (PR) (N = 11) or CR (N=26) on interim CT or PET-CT scan. Of these 37 cases, one patient died of neutropenic sepsis, whilst 36 remain alive with 35 in complete remission. 30 of these 37 patients had CT scan and/or PET-CT scan at EOT: 27 were in CR, 2 were in stable PR and 1 patient (in CR on interim PET -CT scan) showed relapse on PET-CT scan. 16 patients in CR at EOT had 55 follow up surveillance scans (median 2, range 1-8) -two further relapses were detected on PET-CT scan, both 4 months after EOT. Two of the relapsed cases are in CR following further chemoimmunotherapy and allogeneic stem cell transplant whilst the other relapsed case is currently responding to further chemoimmunotherapy.

2 patients without evidence of DH showed disease progression on interim scan and were refractory to further chemotherapy, dying within 3 months and 18 months of diagnosis. All 4 patients with DH lymphoma had PR or CR at interim scan but relapsed within 5 to 8 months after diagnosis and proved chemotherapy refractory with death in 3. One patient with DH lymphoma remains in CR following local radiation and maintenance therapy with rituximab, lenalidomide and metformin.

In our experience, patients with DLBCL, without DH or TH, who have evidence of response to R-CHOP at interim scan have an excellent prognosis. In this patient cohort, 85 EOT and follow up scans detected 3 relapses, suggesting that the detection rate of follow up scans in asymptomatic patients in this good prognosis group is low and of questionable usefulness. The 3 relapsed patients were readily salvageable by further chemoimmunotherapy with or without allogeneic stem cell transplant. In contrast, patients with DH lymphoma or evidence of disease progression on interim scan have very poor prognosis and urgently require alternative therapy approaches.