Relapsed/Refractory DLBCL: Sequencing Therapy


Tycel Jovelle Phillips, MD, of the University of Michigan, comments on his preferences for treating patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and shares his expectations for sequencing with newer, novel approaches emerging in the field.

Tycel Jovelle Phillips, MD: In the primary refractory setting, CAR T [chimeric antigen receptor T-cell therapy] is the ultimate goal. Typically, I would give the patient RICE [rituximab, ifosfamide, carboplatin, etoposide], then attempt to see if we get chemo sensitivity to get them to an autologous stem cell transplantation. Early on, if I don’t notice any response to therapy, I will sometimes scan these patients, even at the first line of therapy, and see if there’s any significant reduction. At that point, I would give these patients polatuzumab and refer them for CAR T. I don’t give bendamustine out of concern of being able to harvest the patients’ T cells. Once the apheresis process is over, if they still need to give more of a bridging therapy, I will add bendamustine back. The hope is that a couple cycles of polatuzumab will get them to the point where the CAR cell is ready, and I would then take these patients to CAR T. 

If those patients fail post-CAR T, we’ve been enrolling these patients in studies with bispecific antibodies. If the antibodies do not fail, we try additional chemotherapy studies. Or, depending on what we gave as a bridge, we’ve tried pola-BR [polatuzumab vedotin in combination with bendamustine and rituximab], and we’ve tried len-tafa [tafasitamab plus lenalidomide] on these patients. Again, loncastuximab is just getting approved, so we haven’t attempted to use that thus far in this patient population.

For patients who are not eligible for a CAR product, or eligible for an autologous stem cell transplantation, we would attempt to enroll these patients in a clinical trial. If it is a standard clinical practice, based on their ability to get covered for lenalidomide, then we would use len-tafa in these patients in the second-line setting. If len-tafa is something we can’t get, GEMOX [gemcitabine in combination with oxaliplatin] is an option for these patients. If the patient can’t tolerate GEMOX, then, based on the approval, we would look into loncastuximab as an option for this patient population.

Our utilization on Selinexor, given the low overall response rate, would be a last resort in a young patient who I’ve exhausted all other options with, but I can’t see that comparing with the other drugs, given the patient population and the overall outcome at this point. However, the goal is CAR T, for the patient who is auto-eligible and CAR-eligible, and thereafter it’s clinical trials or some of the other agents. The preference for len-tafa in this situation is because, in a second-line setting, the data are much more impressive. Additionally, we don’t have the data about some of these other agents thus far in the second-line setting, but I would suspect at least loncastuximab would have a good response rate. It would be something I’d look forward to seeing.

In the future, Selinexor will have to be given in a combination. I’d also be curious to see when the bispecific [antibodies] come onto the market, where they would fit into this situation, given the unique mechanism of action and off-the-shelf T-cell directed therapy at this point.


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