ASH 2014

HIV-associated lymphoma responds well to stem cell transplantation

Dr Joe Alvarnas - City of Hope National Medical Center, Los Angeles, USA

One of the things that it’s done is it’s almost numbed us to the fact that HIV is still a very significant virus and still causes people problems, even though their HIV may be very well controlled. So up to 10% of patients with HIV infection who have the disease controlled may still develop lymphoma and the risk of lymphoma is 25 times higher in this patient population than it is in the non-infected patient population.

Can you explain to me, then, what has been happening in guidelines because HIV infected patients are quite frequently excluded from autologous transplantation, aren’t they?

Sure and I think part of that reflects what we’ve been trying to get a handle as to how best to manage patients with HIV infection and underlying malignancies. So prior to the availability of HAART or cART therapy patients did very poorly; they tolerated standard therapies not at all; they often succumbed to other infection or to progression of the lymphoma. After the advent of HAART therapy you’ve seen a progressive escalation in the intensity of therapy to the point where patients are now treated with the same standard regimens that they have yet there has been a certain conservatism in moving people on to transplant. So part of it has been inertial, part of it has also been how do you manage patients through the process of a very intensive chemotherapeutic regimen while acknowledging that some degree of immunosuppression still exists as a result of HIV infection.

Right, so what did you do in the study that you’ve just reported?

I’d say we did three things. First we didn’t let that historical reticence be a barrier to moving forward with the transplant. The second is that we made sure that we used a consistent transplant regimen and a consistent strategy for managing HIV throughout the course of patient care, which has not been done consistently in prior trials. The third thing that we did is that we selected patients to ensure that they had treatable HIV infection. They either had significant suppression of viral load or were still sensitive to HIV medications so that those patients who were at the worst risk for complications related to transplant were excluded through appropriate selection.

So could you tell me about the study, the protocol, what the patients were like, what happened?

Sure. Yes, we initially enrolled 43 patients with HIV related lymphomas, either non-Hodgkin lymphoma or Hodgkin lymphoma. These patients needed to show that they had treatable HIV infection, they needed to have relapsed or refractory lymphoma but those that were still sensitive to chemotherapy treatment. All the patients mobilised blood stem cells without difficulty, there was no-one who failed to mobilise stem cells, and the patients were treated with a consistent regimen of BEAM, that’s carmustine, etoposide, cytarabine and melphalan. What we did afterward is that we had a period of interruption in the anti-HIV therapy between the time that they began their chemotherapy, the BEAM regimen, through the time when their nausea, vomiting, mouth sores, had resolved from therapy so that we tried to limit the interruption in anti-HIV therapy. Then we allowed these institutions, sixteen in total across the country, to use their standard of care for support post-transplant.

So you harvested the cells, you gave them the chemotherapy as you would with any patient having autologous transplantation, what were the results?

They were rather extraordinary. First we did not see a plethora of weird opportunistic infections. Instead, we saw the patients engraft in a timely fashion, have adequate haematopoietic recovery and in fact we saw some rather extraordinary tumour responses - 93% of the patients were in complete remission by day 100 post-transplant. The other thing that we saw was that the patients tolerated therapy well and at the conclusion of one year, that is after a median observation of 24 months, our projected one year overall survival was 86.6%.

So the effectiveness in combatting lymphoma was as good as it would be if they did not have HIV?

That’s an excellent question. We actually took a step further following the conclusion of this part of the study and our statisticians identified 151 age, gender, lymphoma and disease status matched controls from the CIBMTR registry and compared them and there was no statistically significant difference between treatment related mortality, infection, progression or other parameters. In fact, when you look at the survival curves they were not statistically significantly different.

What are your conclusions from this?

My conclusions are threefold. First, for someone with HIV related lymphomas we need to make sure that they get access to appropriate care, to the standard of care. So I would consider autologous transplant in the same fashion that I would for someone who is not HIV infected. The second thought is that for patients participating in clinical trials beyond the standard of care we shouldn’t let HIV in and of itself be a barrier to patients participating in clinical trials. Then thirdly we want to make sure that as we evaluate patients for lymphoma risk, for the development of disease, that we also make sure to attend to their HIV infection, that it’s treated effectively throughout their course of care so that we can offer more of these patients transplant and other therapies in a timely, effective and efficient manner.

So what would you say to cancer doctors right now about how they should change their therapy today?

You should consider HIV patients in the same way that we’d consider patients without HIV infection and be ready to offer them autologous transplant if they qualify otherwise.

Quick bottom line message?

If they need a transplant, do a transplant.