Do you intensify treatment for patients with double-hit lymphoma or double expressor lymphoma?

My personal practice is that I DO intensify therapy for patients with DHL but not necessarily with DE lymphoma. Generally, the "intensification" of choice is based on age. Young fit patients (for which there are few) with DHL are candidates for CODOX-M/IVAC or DA-REPOCH. Older patients (which the majority of DLBCL patients are) get DA-REPOCH. I think data clearly suggests at this point that outcomes with RCHOP in DHL are poor. As a result, we've gone to using regimens more commonly used with Burkitt Lymphoma - still no clear winner with what the "best" therapy is in this situation though. CNS prophylaxis is essential. One of the challenges with DHL and DE lies in effectively being able to screen patients - and accurately identifying cell of...

This is an excellent and hotly debated question in the lymphoma literature. For patients with double hit lymphomas (who make up ~10% of DLBLC, it is still my practice to treat with DA-R-EPOCH. For those with high IPI (which almost all do) or renal/adrenal involvement, I also give CNS prophylaxis.

For those with double expressor lymphomas (who make up ~30% of DLBCL), I have become more inclined to give R-CHOP. I agree with @Dr. First Last that these patients often have an activated B-cell or non-GCB phenotype. Especially given that the CALGB/Alliance 50303 study has not demonstrated an improvement with DA-R-EPOCH, it seems that if there were a small benefit to dose intensified approaches in these patients, it would likely be small. I have a...

TREATMENT OF RELAPSED DHL

First determine cell of origin

Lenalidomide and Ibrutinib can be considered. Both cross the blood brain barrier.

Morschhauser F et al. A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid^®) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: The EXPECT trial. Eur J Cancer 2013;49(13):2869-76. Abstract

Lunning MA et al. A phase I/II trial of the combination of romidepsin and lenalidomide in patients with relapsed/refractory lymphoma and myeloma: Phase I results. Proc ASCO 2014;Abstract 8582.

Nivolumab is another option.

(Lesokhin et al, JCO 2016;34:2698)

Double-expressing lymphoma (IHC positivity of MYC and either BCL2 and/or BCL6) can be of either non-germinal center or germinal center immunophenotype, although more commonly will be non-GC. While DEL is an adverse prognostic factor, there is no convincing evidence at this time that treatment should be changed in the face of DEL status beyond what would have been recommended for the DLBCL itself, including choice of induction regimen and possible CNS prophylaxis.

There is an ongoing clinical trial (NCT03984448) which is testing whether the addition of venetoclax to R-CHOP in double expressors and venetoclax to DA-R-EPOCH in double hit will improve outcomes, PFS primary endpoint, OS secondary endpoint.