Targeted treatments for diffuse large B-cell lymphoma

This study reviewed the use of targeted therapies in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive non-Hodgkin lymphoma. The standard treatment for DLBCL is the chemoimmunotherapy combination R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). However, 30% to 40% of patients will relapse or will not respond to treatment.

New methods of genetic testing have shown that there are multiple subtypes of DLBCL. 50% of patients have germinal center B-cell (GCB) DLBCL. 30% have activated B-cell (ABC) DLBCL. New treatment options are becoming available that target these specific genetic subtypes.

The current study reviewed targeted treatments under investigation for different subtypes of DLBCL.

Bruton’s tyrosine kinase (BTK) inhibitors, such as ibrutinib (Imbruvica), target the protein BTK. BTK is involved in cancer cell growth. In a trial examining the use of ibrutinib in relapsed or refractory (did not respond to treatment) DLBCL, a 41% response rate was noted in patients with ABC-DLBCL. However, patients with GCB-DLBCL did not respond to this treatment.

Enzastaurin (LY317615) inhibits the PKC-beta protein. In one trial, 71% of patients treated with enzastaurin and R-CHOP were progression free after 1 year. In comparison, 52% treated with R-CHOP alone were progression free. A larger study, however, did  not show improvement in time to disease progression.

Proteasome inhibitors, such as bortezomib (Velcade), block a molecular process that can lead to cancer cell growth. Results of studies examining bortezomib have been mixed. One study noted a significant improvement in response rate in patients with ABC-DLBCL (83%) compared to GCB-DLBCL (13%), with longer survival. However, another study did not find any differences between the subtypes.

Lenalidomide (Revlimid) is an oral immunotherapy that stimulates the immune system to fight against cancer cells. One study examining records of patients treated with lenalidomide showed a significantly higher response rate in patients with non-GCB-DLBCL (52.9%) compared to GCB-DLBCL (8.7%). Other trials have noted that lenalidomide combined with R-CHOP was effective and safe in elderly patients. Another study noted a 98% response rate when lenalidomide was combined with R-CHOP. 80% of patients saw complete response (no sign of disease).

Everolimus (Afinitor) and temsirolimus (Torisel) are treatments that block the protein mTOR. When used on their own, they have shown a 25%–30% response rate in non-Hodgkin lymphoma (including DLBCL). A 38% response rate was noted when these treatments were combined with rituximab.

Studies are also looking at the use of the immunotherapies nivolumab (Opdivo) and pembrolizumab (Keytruda), as well as the modification of certain immune cells (CAR-T cells) to fight against DLBCL.

This study reviewed current and future targeted treatments for different subtypes of DLBCL.