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Just In... Meeting News
Key news updates from recent oncology and hematology meetings.

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Thursday, December 25, 2014

 

BY ED SUSMAN

 

SAN FRANCISCO – When pulmonary emboli are found on incidental imaging scans performed in cancer patients, anticoagulation reduces the risk of recurrence, researchers reported here at the American Society of Hematology Annual Meeting.

 

In a retrospective study that included outcomes in 926 cancer patients, Tom van der Hulle, MD, a researcher at Leiden University in the Netherlands, said that not treating these asymptomatic patients was associated with about twice the risk of developing a subsequent clot (Abstract 590).

 

That risk of recurrent venous thrombosis was about 12 percent in patients who received no treatment compared with 6.2 percent if patients were anticoagulated with low molecular weight heparin and 6.4 percent if anticoagulated with a vitamin K antagonist such as warfarin.

 

The problem of major bleeding, van der Hulle said, was greater with treatment with warfarin-like treatments--about 13 percent of patients, compared with 3.9 percent of those who received low molecular weight heparin. The

six-month mortality rate was 47 percent among patients who did not receive anticoagulatants, compared with 37 percent of patients on low molecular weight heparin and 28 percent of those on warfarin.

 

“Our findings suggest that anticoagulant therapy after incidental pulmonary embolism findings may reduce the risk of clot recurrence in cancer patients,” he said.

 

In a news conference at the meeting highlighting noteworthy abstracts on managing blood clots and preventing recurrence, he said that blood clots in the lungs detected on computed tomography scans conducted for other purposes – these so-called incidental pulmonary emboli -- are an increasing complication affecting cancer patients. He said that when doctors review scans for staging of patients or for evaluating treatment, they will often observe clots in the lungs and that the prevalence of these asymptomatic clots in the lungs is about three percent.

 

But even though such clots are relatively common, knowledge about their prognosis, optimal management, and recurrence risk has been scarce, which was the reason for the retrospective analysis that included 11 reports or registries. The study team focused on outcomes after six6 months following the discovery of the blood clots.

 

Feasibility for RCT?

“While we previously had no evidentiary basis for anticoagulating cancer patients with incidental pulmonary embolism, this study provides a strong argument for always treating this population to prevent recurrence,” he said. “Ideally, our findings should be confirmed in a randomized clinical trial. However, given our current and previous results, we believe that it would be ethically challenging and perhaps unfeasible to design a trial allocating patients with cancer-associated incidental pulmonary emboli to placebo.”

 

Van der Hulle said the findings support current treatment guidelines for treatment of incidental pulmonary embolism, which is basically the same treatment – anticoagulation therapy – for patients with symptomatic pulmonary embolism.

 

He suggested that treatment with vitamin K antagonists or low molecular weight heparin for at least six months should continue as long as the cancer in the patients is active.

 

Agnes Y.Y. Lee, MD, Medical Director of the Thrombosis Program and Associate Professor of Medicine at the University of British Columbia, who also presented research on treatment of blot clots in cancer patients (page XXX), said: “Blood clots are more often seen in treatment of patients with pancreatic cancer, lung cancer, and gastrointestinal cancers. We know that even when these cancers are being actively treated there remains a risk of blot clots. We know that if we stop anticoagulation therapy the risk of pulmonary embolism will be much greater.”

 

After three to six months of treatment, if the patient is clear of cancer or the disease is in remission and the patient is no longer receiving chemotherapy then anticoagulation therapy can be discontinued, she said.

Van der Hulle said that evidence is lacking for when to discontinue treatment if patients still have active cancer.

 

Objectively Very Difficult to Treat These Patients

The moderator of the news conference, Mary Cushman, MD, Professor of Medicine in the Hematology/Oncology Division at the University of Vermont, commented that it can be extremely difficult to treat such patients: “There are patients with cancer whose clinical course is very indolent and their cancer is not very active, so for those types of patients it might be appropriate to stop or switch to a lower intensity of treatment or to use it prophylactically. But we really have no randomized clinical trials in this setting to help us, so we have to use our knowledge and clinical judgment. This can be quite complicated.

 

“Despite the progress in providing options for treatment for patients with blood clots, the challenges persist of managing the risk and benefits of treatment, because any time you thin a person’s blood you have a risk of bleeding,” she continued.

 

“While the treatments can reduce the risk of clotting, severe bleeding can occur. The study gives physicians and researchers important new information with which to weigh the treatment option that they have in preventing thrombosis and in treating thrombosis and really will set the stage for future work that will continue to improve the health of our patients. ”

 

Van den Hulle said that of the 926 patients included in the analysis, 79 percent were treated with low molecular weight heparin, 11 percent received vitamin K antagonists, and six percent of patients with incidental, asymptomatic emboli were left untreated. Most of the patients had been diagnosed with metastatic cancer.

 


Thursday, December 25, 2014

 

By Robert H. Carlson

 

San Francisco--Cancer patients who have venous thromboembolism (VTE) have a substantial risk of having recurrent VTE, and low molecular weight heparin (LMWH) is recommended in the National Comprehensive Cancer Network and American Society of Clinical Oncology consensus guidelines as the preferred anticoagulant, rather than warfarin.

 

But the evidence for that is based largely on one clinical trial published in 2003, the open-label randomized “CLOT” trial—i.e., Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer—led by Agnes Y.Y. Lee, MD, Medical Director of the Thrombosis Program and Associate Professor of Medicine at the University of British Columbia, published in the New England Journal of Medicine (2003; 349:146-153).

 

A new study with 900 patients, also led by Lee, was conducted to determine whether the guidelines are supported by better data, and she presented those results here as a late-breaking abstract at the American Society of Hematology Annual Meeting (Abstract LBA-2). The trial, called CATCH--Comparison of Acute Treatments in Cancer Haemostasis--found that although the LMWH tinzaparin lowered the risk of recurrent VTE compared with warfarin, with a significant reduction in symptomatic deep vein thrombosis (DVT) and clinically relevant non-major bleeding, there was no difference in major bleeding or overall mortality.

 

The randomized, open-label, multicenter, Phase III study compared the use of tinzaparin with heparin in preventing recurrent VTE in patients with active cancer and acute, symptomatic proximal DVT and/or pulmonary embolism (PE).

 

Patients were stratified by geographic region, tumor characteristics (distant metastasis, no distant metastasis, hematological malignancy), and history of VTE. Patients were randomly selected to receive either tinzaparin at 175 IU/kg once daily for six months or initial tinzaparin at 175 IU/kg once daily for five to 10 days overlapped and followed by dose-adjusted warfarin (target INR 2.0-3.0) for six months.

 

The primary efficacy outcome was time to recurrent VTE, a composite endpoint that included symptomatic DVT and/or PE. The primary safety endpoint was the incidence of major bleeding. All patients were followed for six months or until death.

 

The 900 patients were from 165 sites in 32 countries. Of these, 449 were randomly selected to receive tinzaparin and 451 to warfarin. The patients’ mean age was 59, 59 percent were female, 77 percent had a baseline ECOG performance status of 0-1, and 23 percent had a performance status of 2.

 

The most common primary tumor sites were gynecologic (23% of patients), colorectal (13%), lung (12%), breast (9%), and hematologic (10%). Metastatic disease was present in 55 percent of patients, and 44 percent had received prior cancer treatment.

 

Time in therapeutic range was 47 percent in the warfarin arm, with 27 percent above and 26 percent below the range.

 

Primary Outcome Not Statistically Significant

Over the six months of the study, 31 patients (7.2%) in the tinzaparin arm experienced recurrent VTE compared with 45 (10.5%) in the warfarin arm, for a hazard ratio of 0.65. There were two patients with incidental VTE, both in the warfarin arm.

 

Symptomatic non-fatal DVT occurred in 12 patients (2.7%) in the tinzaparin arm versus 24 (5.3%) in the warfarin arm, a 52 percent decrease.

 

Symptomatic non-fatal PE occurred in three patients in the tinzaparin arm and two in the warfarin arm. But the rate of fatal PE was identical--17 patients (38%) in each arm.

 

There was no also difference in the incidence of major bleeding events: 13 (2.9%) for tinzaparin versus 12 (2.7%) for warfarin, although significantly fewer patients had clinically relevant non-major bleeding with tinzaparin: 50 patients (11%) versus 73 patients (16%) on warfarin. And no statistically significant difference was seen in six-month survival rates--59 and 60 percent, respectively.

 

‘Clearly Disappointed’

Lee said the researchers were clearly disappointed that the primary outcome did not achieve statistical significance. “Our sample size was based on an estimated recurrence rate of 12.6 percent in the warfarin group, but we saw only a 10 percent recurrence, so we thought the trial was slightly underpowered. Given the symptomatic DVT results [in CATCH], in addition to all of the previous data available on LMWH, this is still very strong confirmatory data that LMWH is more effective than warfarin for treating cancer patients.”

 

In a teleconference for reporters before the meeting, ASH Secretary Stephanie J. Lee, MD, MPH, Professor of Medicine at the University of Washington and a member of Fred Hutchinson Cancer Research Center, said the study supports the consensus recommendation to use LMWH in cancer patients who have clots.

 

We’ve always been worried that patients who have cancer may be less responsive to warfarin in that population,” she said. “We also know the rate of recurrence is very high in that population -- they are predisposed to thrombosis, are often immobile, and are getting chemotherapy drugs that may affect their thrombostatic state; it’s a very, very high-risk population for both thrombosis and bleeding.”

 

One of the co-moderators of the Late Breaker Session was less sanguine about the CATCH results: “It's probably a reasonable approach [LMWH in cancer patients],” said Margaret Ragni, MD, Professor of Medicine in the  Division of Hematology/Oncology and Director of the Hemophilia Center of Western Pennsylvania at the  University of Pittsburgh Vascular Medicine Institute. “But with 900 patients [the advantage in preventing VTE] is still not quite statistically significant, and we need to learn more.”

 

Ragni said her biggest concern with the trial was the time in the therapeutic range for patients on warfarin: “Only 47 percent of the time were they on the drug, so the question is, what are we seeing here?” Ragni asked Agnes Lee after her presentation. Lee responded that warfarin is a difficult drug to administer and that was the best that could be done. Time in therapeutic range in the CLOT study was similar, at 46 percent, she said.

 

“Although these numbers seem very low, this is probably as good as it gets for patients on chemotherapy taking warfarin.”

 

After the presentation, Ragni commented that that might change when the new oral anticoagulants are introduced: “Then it will be as good as it gets, so stay tuned.”


Wednesday, December 24, 2014

 

By Robert H. Carlson

 

San Francisco – The value of maintenance therapy in treating hematological malignancies is being weighed in many arenas, but compliance is a concern.

 

In multiple myeloma, the proteosome inhibitor bortezomib has a solid place in several regimens but it is administered subcutaneously, certainly more convenient than intravenous administration as when the drug was first introduced, but patients still have to return to the clinic for weekly injections.

 

Now, though, a Phase II study of the safety and tolerability of the first oral proteosome inhibitor ixazomib (MLN-9708) showed an increasing depth of response with long-term use following an all oral induction regimen of ixazomib-lenalidomide-dexamethasone in patients with previously untreated multiple myeloma, as reported here at the American Society of Hematology Annual Meeting (Abstract 82).

 

“The takeaway message is that we have a completely oral triplet regimen for treating myeloma and that this new drug can be given on a long-term basis that potentially provides long-term disease control,” said Shaji K. Kumar, MD, Professor of Medicine at Mayo School of Medicine, who presented the results, speaking in an interview before the meeting.

 

“The field is moving towards more prolonged treatment of multiple myeloma. The old concept was that we would treat the disease for x number of cycles, or months, and then stop and watch. But increasingly we are learning that a subgroup of patients may benefit from continuing treatment for a prolonged time--maybe two to three years, or even until progression.”

 

Weekly ixazomib plus lenalidomide-dexamethasone had been investigated earlier in a Phase I/II trial as triplet induction therapy followed by single-agent ixazomib maintenance therapy. The new report covers Phase II efficacy and safety data in patients receiving ixazomib maintenance.

 

Study Details

A total of 50 patients were enrolled, with 29 discontinuing during induction, primarily to undergo stem cell transplant (14 patients), due to adverse events (6 patients) or patient withdrawal (4 patients).

 

Twenty-one patients received ixazomib maintenance therapy, and the median treatment duration for both induction and maintenance was 26.6 months.

 

Among the 49 evaluable patients, 44 (90%) achieved at least a partial response or better, including 29 (59%) who had very good or better responses.

 

“All 21 patients who received ixazomib maintenance had responded to induction therapy,” Kumar said. Overall responses in the 21 patients included complete responses in 11 (52%).

 

During maintenance, 33 percent of patients improved their response, including two very good partial responses that improved to near complete response, and five very good partial responses that improved to complete response.

 

Kumar noted that there is a lot of experience with bortezomib-lenalidomide-dexamethasone, one of the most effective combinations, as well as with combined carfilzomib and lenalidomide-dexamethasone, which is also very effective: “So it made sense to examine how ixazomib would combine with lenalidomide and dexamethasone in a completely oral combination.”

 

Oral ixazomib, therefore, he said, avoids the inconvenience of bortezomib, part of the backbone for many myeloma treatment regimens, which is given by subcutaneous injection once a week.

 

“Clearly there was a great need for an oral proteosome inhibitor, especially given the fact that the other major class of drugs for multiple myeloma, immunomodulatory drugs like lenalidomide and pomalidomide, are oral drugs taken once a day,” Kumar said. “Ixazomib is the first to fill in that space.

 

“These data indicate that single-agent ixazomib maintenance for up to one and a half years was feasible and generally well tolerated, improved responses following ixazomib-lenalidomide-dexamethasone induction, and contributed to durable responses with a  median of more than two years in previously untreated myeloma patients not undergoing stem cell transplant.”

 

Paul Richardson: ‘Reassuring Tolerability’

Paul Richardson, MD, Director of the Myeloma Program at Dana-Farber Cancer Institute and the study’s senior author and the moderator of the oral session where the paper was presented, called the data “extraordinary” and the tolerability “very reassuring.”

 

Selecting Out Patients

Another expert, Saad Usmani, MD, Director of Clinical Research in Hematologic Malignancies and Head of the Myeloma Program at Levine Cancer Institute, was asked for his perspective for this article: “If you can prove equal or better efficacy without a lot of side effects, then oral medicines make sense,” he said, noting, though that patients in the trial were not bortezomib refractory or resistant, and the study researchers selected out patients who were not exposed to or had not become resistant to proteasome inhibitors.

 

“I think that’s the key feature,” he said.

 

The oral availability aspect is important, he said, “but you are selecting out patients who may still be sensitive to proteasome inhibition.”


Wednesday, December 24, 2014

 

By Robert H. Carlson

 

SAN FRANCISCO-- Are anti-CD38 monoclonal antibodies the next blockbusters in treating multiple myeloma? That was the appraisal of several experts here at the American Society of Hematology Annual Meeting.

 

“I think these CD38 antibodies are the new blockbuster drugs for multiple myeloma,” said Thomas G. Martin III, MD, Clinical Professor of Medicine in the Adult Leukemia and Bone Marrow Transplantation Program and Associate Director of the Myeloma Program at the University of California, San Francisco. “Antibodies have worked very well with drugs like rituximab in lymphoma, but in myeloma we're 10 years behind. Finally we have some that work.”

 

Martin presented trial data on the anti-CD38 agent SAR650984; and data from another anti-CD38 agent, daratumumab, were reported by Philippe Moreau, MD, Head of the Hematology Department at University Hospital of Nantes, France.

 

Daratumumab, SAR650984, MOR202

Martin explained that there are currently three anti-CD38 antibodies under investigation for multiple myeloma--daratumumab, SAR650984, and MOR202. All bind to a different part of the CD38 receptor, “but whether that makes any clinical difference we don't know at this time.”

 

He said the humanized IgG1 monoclonal antibodies bind selectively to the CD38 receptor and “flag down the immune system.”

 

A blockbuster would be an agent with significant single-agent activity in the front-line setting that also combines effectively with proven agents in the relapsed/refractory setting, he said. “With the two 'blockbuster' classes of drugs we have now, the immunomodulators [IMiDs] and the proteosome inhibitors, we have advanced the overall survival of patients with myeloma, from potentially three years to seven to 10 years, although in a more heavily pretreated population, such as the patients in these two trials, the average survival is less than one year.”

 

Martin presented Phase Ib data from the TCD11863 dose-escalation trial of SAR650984 combined with lenalidomide and dexamethasone (Abstract 83), which was funded by Sanofi. At nine months' follow-up the overall median progression-free survival time was 6.2 months, and median progression-free survival had been not reached.

 

He said this was a promising combination because SAR650984 stimulates the immune system while lenalidomide is an immunomodulator.

 

Preclinical studies showed synergy between SAR650984 and lenalidomide, he said, and use of the former as a single agent in a similar group of patients produced an overall response rate of approximately 30 percent.

 

This was a heavily pretreated population, with no upper limit on prior therapies, Martin pointed out. The median number of prior regimens was seven with four median prior lines of therapy, and all patients did have adequate bone marrow reserve at study entry.

 

A total of 94 percent of patients had received prior lenalidomide; 94 percent, prior bortezomib; 29 percent, prior Pomalidomide; and 48 percent had prior carfilzomib.

 

“Many of these patients were what we consider 'double refractory'—i.e., refractory to our most potent blockbuster drugs,” he said.

 

The starting regimen was 3 mg/kg every other week with standard doses of lenalidomide and dexamethasone, increasing to 10 mg/kg every other week.

The regimen was well tolerated with no unexpected toxicities, Martin said, although there were infusion reactions often seen with antibody agents. Those led two patients to discontinue treatment--one with a serious anaphylactic reaction and the other with non-serious maculopapular rash.

 

Most infusion reactions were seen in cycle 1, and none after cycle 2. The response rate in the 31 patients treated was 58 percent at nine months follow-up, with a clinical benefit rate of 65 percent (including minor responses).

Overall response in the 24 patients who received the highest dose (10 mg/kg) was 63 percent, which Martin pointed out was double the single-agent response rate. These included two stringent complete responses.

 

The overall response rates were 50 percent in the 26 patients who were relapsed or refractory to IMiDs, 40 percent in the 15 patients refractory to carfilzomib; and 33 percent in the nine patients relapsed/refractory to pomalidomide. Median progression-free survival was 6.2 months.

 

Martin said the pharmacokinetics of SAR650984 and lenalidomide appear to be independent of each other.

 

“This combination was well tolerated, and in my mind had a fairly dramatic response with two-thirds of the patients having responses.

 

“The next five years are going to be really fun, moving these drugs from the refractory setting to the less refractory setting to front line. It's going to be really exciting.”

 

The next step will be a randomized trial of SAR650984-lenalidomide-dexamethasone versus lenalidomide-dexamethasone to compare outcomes, he said.

 

Paul Richardson: ‘Remarkable Results’

After Martin's presentation, session co-moderator Paul G. Richardson, MD, Clinical Director of the Jerome Lipper Myeloma Center at Dana-Farber Cancer Institute, called the results remarkable, especially given the short follow-up of nine months “and already seeing a progression-free survival of 6.2 months.”

 

“It could well be you'll see a really striking PFS advantage overall,” Richardson said.

 

Martin said he thought the progression-free survival may not change very much but that the duration of response may indeed improve. Richardson suggested that an IMiD might be the best to combine with SAR650984, for a co-immune-stimulatory effect, and Martin agreed.

 

Martin was asked to comment on the SAR650984 maximum tolerated dose (MTD), which had not been reached.

“I don't know what Sanofi has planned, but I would love to increase the dose of SAR, double or even triple it,” he answered. “That may help with progression-free survival and duration of response.”

 

Daratumumab Tested with Backbone Regimens

European researchers in the MMY1001 trial hypothesized they could potentially improve response rates for the anti-CD38 antibody daratumumab by combing it with a standard regimen, so they combined it with four standard regimens: bortezomib-dexamethasone (received by six patients), bortezomib-thalidomide-dexamethasone (also six patients), bortezomib-melphalan-prednisone (also six patients), and pomalidomide-dexamethasone (seven patients) (Abstract 176).

 

The 25 patients in this four-arm, open-label Phase Ib trial, which was sponsored by Jansen Research & Development, were had newly diagnosed, relapsed, or refractory disease. The dose of daratumumab for all patients was 16 mg/kg.

 

Moreau reported safety data in the trial of 17 patients in the three bortezomib arms. At a median of 44 days there were infusion-related reactions, which did not interrupt treatment, but no unexpected adverse events. Although this was a safety trial, he was able to report overall response rates of 100 percent in the newly diagnosed group and 50 percent in the relapsed group.

No patients receiving front-line treatment achieved a complete response, but there was one complete response in the pomalidomide arm. All responses were seen in cycle 1, and median time to first response was approximately 25 days.

 

Because of the small size of this study, the response rates are probably underestimated, Moreau said. “By targeting a simple molecule expressed by the cancer cells, this therapy has the potential to become a potent addition to conventional treatment.”

 

Patients Eager to Enroll

At a news conference at the meeting highlighting newsworthy lymphoma and myeloma abstracts, Martin was asked what these trial results might mean to community oncologists. He said it should encourage them to refer appropriate patients to clinical trials – if their patients haven't already called the researchers themselves: “Most of the time patients were calling us, because they know about these trials,” he said.

 

“We finished our trial in record time, about 10 months, because doctors were literally on the line fighting to get their patients on the trial. This is where it's at.”

 

Also at the news conference, the moderator, Brad Kahl, MD, Clinical Research Director of Hematologic Malignancies at the University of Wisconsin Carbone Cancer Center, was asked whether the data on the anti-CD38 agents supported their “blockbusterness.”

 

“These are small trials, and it's too early to plant the victory flag in the ground, but all that's been said about them is totally justified regarding bringing them to front-line setting,” he replied.

 

‘Phenomenal Responses in Small Expansion Cohort’

Asked his opinion for this article, Saad Usmani, MD, Director of Clinical Research in Hematologic Malignancies and Head of the Myeloma Program at Levine Cancer Institute, said that both SAR650984 and daratumumab appear to be quite effective in the relapsed/refractory myeloma setting as single agents and in combination with some of the other approved myeloma drugs, but the SAR650984 trial was unique in that all patients enrolled were refractory to lenalidomide.

 

“They’re trying to tease out the effect of the anti-CD38 in this patient population--whether adding the SAR drug will help potentiate that somehow,” he said. “And that’s what the study shows. In a small expansion cohort of 18 patients they are seeing phenomenal responses with this combination, with an overall response rate somewhere in the 63-percent range for a very refractory patient population.

 

“Anti-CD38 monoclonal antibodies are by far the most exciting drugs that are in development in multiple myeloma.

 

The challenge with monoclonal antibodies is the infusion time and the schedule, he noted. “It takes several hours to give them, the first time it may take up to six hours, although the subsequent infusions can be reduced to three-and-a-half to four hours. That’s the challenge for these drugs, to figure out the schedule – once a week, every other week? – and how long to give it.

 

“The Phase I study with daratumumab was essentially a safety-generating study to justify using daratumumab with other available anti-myeloma therapies, the common backbones we utilize for myeloma. This was a safety not efficacy trial, but it does add to the efficacy of the combination.”


Sunday, December 21, 2014

 

BY ROBERT H. CARLSON

 

SAN FRANCISCO--Patients with HIV-associated lymphoma can undergo hematopoietic cell transplant as safely as non-HIV lymphoma patients, despite conventional wisdom that they are at higher risk of infection and poor graft function due to compromised immune systems.

 

Until now, the evidence has been scarce since patients with HIV have been routinely excluded from clinical transplant trials, said Joseph Alvarnas, MD, Associate Clinical Professor and Director of Medical Quality and Quality, Risk, and Regulatory Management at City of Hope, who presented data from a new trial at the American Society of Hematology Annual Meeting. The study (Abstract 674) showed equivalent outcomes for lymphoma patients whose HIV levels are controlled with highly active antiretroviral therapy (HAART) and for non-infected lymphoma patients.

 

“Patients with chemotherapy-sensitive, relapsed/refractory HIV-related lymphoma may be successfully treated with the modified BEAM regimen [BCNU, etoposide, cytarabine, and melphalan], and should be considered candidates for autologous stem cell transplant if they meet standard transplant criteria,” said Alvarnas, who is also Director of Quality Systems for Cellular Therapeutics, Hematology & Hematopoietic Cell Transplantation. “Exclusion of these patients from clinical trials of Hodgkin or non-Hodgkin lymphoma is no longer justified.”

 

The multicenter, Phase II Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0803/AMC 071 trial of autologous hematopoietic cell transplant for chemotherapy-sensitive, relapsed/refractory HIV-related lymphoma showed an overall survival rate of 86.6 percent at 24 months for HIV-infected patients, virtually the same as the 87.7 percent for controls.

 

At 100 days post-transplant, 36 of the 40 patients (92%) had achieved a complete response, one (2.6%) had a partial remission, two (5%) had relapsed, and one patient died.

 

In his presentation, Alvarnas emphasized the “controlled” qualifier for HIV infection.

 

HAART to CART

HAART, introduced in 1996, has improved the prognosis for patients with HIV-associated lymphoma and permitted treatment identical to that in uninfected patients, Alvarnas explained. But the role of autologous hematopoietic cell transplant in HIV-infected patients has been uncertain, even though the risk of non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) in HIV-infected patients is as much as 17 times higher than that for non-infected individuals, even with HAART.

 

“Autologous stem cell transplant was extended to HL and NHL patients in the late 1990s, but even today HIV infection remains an exclusion criterion for most autologous transplant therapeutic trials, and its availability is limited to centers with HIV-specific expertise,” he said.

 

Combination anti-HIV therapy, or CART (not to be confused with CAR-T--chimeric antigen receptor T cells) is now widely used and produces profound viral suppression, improvement in T-cell immunity, and decreased risk of opportunistic infections, he said.

 

The control data in the new trial is from the BMT CTN 0401 trial of autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma (Vose et al: JCO 2013;31:1662-1668). That trial's primary endpoint was overall survival, with secondary endpoints of progression-free survival, disease-free survival, disease responses, and treatment-related mortality.

 

Of the 43 patients accrued, 40 underwent autologous transplant. The three who did not have a transplant because of lymphoma progression were not included in the study analysis. The patients’ median age was 46.9.

 

“All patients received modified BEAM regimen and blood stem cell grafts, and none of the patients had any difficulty mobilizing stem cells,” Alvarnas said.

 

CART was stopped during administration of the preparation regimen, and then resumed after the nausea and vomiting due to the preparation resolved. All patients received standard supportive care.

 

With a median follow-up of the patients of 24 months, the projected 12-month survival is 86.6 percent, Alvarnas said, and the projected 12-month progression-free survival is 82.3 percent, with a one-year mortality rate of five  percent.

 

Will Change Practice

“I think the impact of this trial is going to be large,” said the moderator of  a news conference at the meeting that featured the study, Brad Kahl, MD, Associate Professor of Medicine at the  University of Wisconsin School of Medicine and Public Health and Director of the UW Lymphoma Service and Clinical Research Director for Hematologic Malignancies at the University of Wisconsin Carbone Cancer Center.

 

Kahl agreed that HIV positivity is exclusionary for receiving stem cell transplants in many centers.

 

“Transplant is the only potential curative strategy for HL or NHL patients, so I think these data will change standard practice at centers that currently exclude these patients,” he said.

 

Since the late 1990s autologous transplant has extended to patients with HIV-related lymphoma in France and in the U.S., Alvarnas said, but studies have been limited and trials have largely been retrospective, with varying preparative regimens, performed largely in centers with HIV-specific expertise, and there with variable management of post-CART therapy.

 

The purpose of BMT CTN 0803/AMC 071 was to determine whether the technology could be expanded to non-specialty centers. It was funded by the National Cancer Institute and the National Heart, Lung and Blood Institute, and performed in collaboration with the BMT CTN, the AIDS Malignancy Consortium (AMC), and the EMMES Corporation, a contract research organization.

 

“This study is unique in that it was a collaborative study conducted in 16 transplant centers, all using a consistent protocol, but few with extensive experience in transplantation for HIV-positive patients,” Richard Ambinder, MD, PhD, Director of the Division of Hematologic Malignancies, Kimmel Cancer Center at Johns Hopkins, and leader of the Johns Hopkins AMC site and the Translational Science Working Group, noted in a news release.

 

“Other single-center studies with HIV-associated lymphoma patients have been conducted previously, as well as a study through the AMC, but those studies were limited to a few centers specialized in treating patients with HIV and AIDS.”