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Highlights from ASCO 2013

The annual meeting of the American Society of Clinical Oncology (ASCO) took place in Chicago from May 31 through June 4, 2013, and the work of several of the Lymphoma Research Foundation's (LRF) Scientific Advisory Board (SAB) members were among the studies presented. Over 25,000 oncology professionals from a wide range of specialties attend the ASCO Annual Meeting each year, making it an important venue for sharing and discussing research with the clinical oncology community. This article covers a selection of the many significant studies in lymphoma research presented during the meeting.

CT Scans Offer Limited Benefit in Detecting Diffuse Large B-Cell Lymphoma Relapse

One of the most discussed presentations at ASCO was not a drug trial, but a study examining the usefulness of regular computerized tomography (CT) scans in detecting relapse in patients with diffuse large B-cell lymphoma (DLBCL). The current standard of care is variable with regard to the use of follow-up CT scans after the completion of treatment. Researchers, including SAB members Thomas Witzig, MD and Thomas Habermann, MD, both of Mayo Clinic, reviewed the experience of 644 patients with DLBCL . Of the 109 patients who relapsed, the overwhelming majority (87 percent) had that relapse detected due to symptoms, an abnormal physical exam, or elevated lactate dehydrogenase (LDH), a protein that can indicate relapse at high levels. Only 12 patients had a relapse detected solely by a scheduled follow-up scan -- 1.5 percent of the total patient group.

The study is consistent with similar studies, including one on Hodgkin lymphoma (HL) which was also presented at ASCO, and questions the usefulness of routine CT scans post-therapy in patients without symptoms. This may spare the patient not only the radiation exposure and general anxiety of more frequent tests but potentially could reduce the cost of patient care. However, the study's presenter, Carrie Thompson, MD of Mayo Clinic, noted that additional clinical trials are still needed to determine the scanning schedule that is most beneficial to patients. [1]

Idelalisib Offers Promise for Patients with Treatment Resistant Non-Hodgkin Lymphoma

Idelalisib (also known as GS1101 or CAL101), an oral drug which blocks the PI3K-delta pathway that supports growth of B-cell and T-cell tumors, was a primary component of several clinical trials presented at ASCO. A study of idelalisib as the first-line treatment given to CLL patients, led by former SAB member Susan O' Brien, MD, of MD Anderson Cancer Center, reported high overall response rates of 97 percent, with 93 percent of patients demonstrating ongoing disease response at 24 months after treatment. The results for the 64 patients who participated supported further evaluation in larger studies. [2]

The drug also appears to be effective for patients whose disease had returned or not responded after earlier treatments. SAB Chair John Leonard, MD, of Weill Cornell Medical College, presented results from a study evaluating the drug's safety and activity as part of a combination therapy (with bendamustine and/or rituximab) in patients with relapsed or refractory (unresponsive to treatment) indolent non-Hodgkin Lymphoma (NHL). Dr. Leonard reported patient response to treatment at 78 percent. 26 percent reported complete responses. Moreover, at 24 months, 69 percent of patients were maintaining their response, with 63 percent seeing no further progression of their cancer. Dr. Leonard noted these results supported the need for the current, larger scale trials of idelalisib in various combinations with other drugs. [3]

Another idelalisib study, involving contributions from SAB member Brad Kahl, MD of the University of Wisconsin, tested the drug specifically in chronic lymphocytic leukemia (CLL) patients whose disease was refractory or had relapsed. It also reported high response rates in patients with a median of five prior therapies, with the study's lead author and presenter, Jennifer Brown, MD of Dana-Farber Cancer Institute, noting a rapid reduction in both tumor size and patient symptoms soon after treatment began. Patients averaged over 17 months without further disease progression , better than the 6-12 months usually averaged by CLL patients receiving their sixth round of therapy. Because the vast majority of CLL patients relapse after initial treatment, idealalisib's promising results in relapsed and refractory patients are even more encouraging.[4] (Additional information on CLL may be found at FocusonCLL.org.)

Obinutuzumab May Be Viable Alternative to More Aggressive Chronic Lymphocytic Leukemia Treatments

A German-based study of the drug obinutuzumab (also known as GA101) suggests it may be an effective treatment for patients whose age or health limits the aggressiveness of available treatments. . Obinutuzumab is part of the anti-CD20 antibody class of drugs; it binds to the CD20 protein in cancer cells with the aim of killing the cells directly. The CLL11 study treated 589 patients with either obinutuzumab in combination with standard chemotherapy drug chlorambucil (Leukeran), rituximab (Rituxan) and chlorambucil, or chlorambucil alone. Patients treated with the obinutuzumab combination had an average rate of 23 months without futher advancement of their disease, compared to 15.7 months for the rituximab combination, and 10.9 months for chemotherapy alone. The study was the largest trial to evaluate treatments for previously untreated CLL in elderly patients and patients with other existing health issues, who are often not strong enough to tolerate existing treatments. It remains unclear how obinutuzumab in this setting compares to rituximab, which will be the subject of further followup in additional patients. [5] Though the CLL11 study is still evaluating the longer term results of its trial, the early results were promising enough for the U.S. Food and Drug Administration (FDA) to name obinutuzumab a "Breakthrough Therapy," which accelerates the FDA review process; they have since accepted the application for the drug's use in CLL treatment for Priority Review.[6]

Lenalidomide (Revlimid) Shows Promise in Relapsed MCL, Ahead of FDA Approval

Lenalidomide (Revlimid), an oral anti-cancer drug already in use for multiple myeloma and myelodysplastic syndrome, was discussed during a poster session as a promising treatment option for mantle cell lymphoma (MCL) patients. SAB members Michael Williams, MD of the University of Virginia, and Andre Goy, MD of Hackensack University Medical Center, presented a detailed analysis of their MCL-001 study, while SAB member Thomas Witzig, MD of Mayo Clinic, was lead author on a combined analysis of three separate studies (including the MCL-001 study) of lenalidomide in relapsed or refractory MCL patients. Both studies demonstrated that lenalidomide, when given independently from other treatments, provided a consistent clinical benefit in patients with relapsed or refractory MCL. One day after the ASCO meeting's conclusion, the FDA announced the approval for the use of lenalidomide in treating MCL patients, making it the first and only oral therapy approved for treatment of relapsed/refractory MCL.[7] (More information about lenalidomide and other MCL treatment options are available at FocusonMCL.org.)

Two Promising New Treatments for Non-Hodgkin Lymphoma and T-Cell Lymphomas

In a poster session, preliminary results from a small scale study of ublituximab (another anti-CD20 antibody) in patients with relapsed or refractory B-NHL were presented. The study, which included a sampling of patients with a variety of NHLs, reported several responses, with two of the 12 patients achieving complete remission. These results have prompted recruitment to begin to larger scale trials to better evaluate the safety and activity of this agent in larger numbers of patients.[8]

In an oral abstract session, SAB member Dr. Owen O'Connor from Columbia University presented results from the BELIEF trial, evaluating belinostat in relapsed or refractory peripheral T-cell lymphoma (PTCL). Patients enrolled in the BELIEF trial were either refractory or had relapsed after at least one prior treatment. Belinostat, which targets a set of proteins crucial to cell development called HDAC, was able to induce complete and partial responses in some of these patients and was tolerable at high intensity doses even in those with poor bone marrow reserve, suggesting it may be a potential new treatment for patients with few other options.[9] (The class of drugs called HDAC inhibitors was previously covered by LRF in February; more information on PTCL is available at FocusonPTCL.org.)

Studies of Novel Targeted Agents Ibrutinib and Brentruximab Vedotin

Two drugs that have received accelerated approval from the FDA, ibrutinib (for NHL) and brentruximab vedotin (for HL), were the subjects of separate studies presented by SAB Member Anas Younes, MD, of Memorial Sloan-Kettering Medical Center. The study of ibrutinib, which has also been designated a "Breakthrough Therapy" by the FDA, was presented at an oral abstract session; it was designed to determine the recommended dose of ibrutinib when used with the drug regimen known as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), as well as test for safety issues. In the 17 patients studied, no significant rise in harmful side effects was found when ibrutinib was added to R-CHOP – a promising sign for this new combination therapy.[10] (LRF previously covered ibrutinib and its effects on DLBCL tumors in late 2012.)

An ongoing large scale study was described of brentruximab vedotin (Adcetris) as the first therapy given to advanced stage Hodgkin lymphoma patients following an autologous stem cell transplant (ASCT) – a treatment strategy that has already received provisional approval in Europe. The randomized, multi-center study is examining the effects of adding brentruximab vedotin to the commonly used drug regimen ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), to measure both the treatment's safety and its relapse and refractory rates against the 20 percent refractory and 35 percent relapse rates that occur with ABVD alone. This trial is still in its early stages.[11] (More information on HL is available at FocusonHL.org.)

Summary: A Look Toward the Future

The studies outlined here are only a fraction of the studies presented during ASCO's Annual Meeting, however, they provide a strong sampling of the work currently being done in lymphoma research, as well as a look at the treatment advances lymphoma patients will hopefully see in the future. Whether it is a refinement of existing standards of care or a new drug for the patient who has exhausted all other treatment options, members of LRF's Scientific Advisory Board are pursuing multiple ways to improve both survival rates and patients' quality of life.

For further updates on promising discoveries in lymphoma research, visit LRF's Research News.

Sources and additional info:

  1. ASCO Daily News – "Surveillance Scans Offer No Benefit in Relapse Detection and Survival in Lymphoma"
  2. Oncology Practice – "Idelalisib and rituximab produce reponses in 97 percent with CLL."
  3. ASCO Daily News – "Idelalisib-Containing Combinations Warrant Further Study in Relapsed/Refractory NHL"
  4. OncLive – "New PI3K-delta Inhibitor Prolongs Survival in Chronic Lymphocytic Leukemia"
  5. ASCO Meeting Library – "Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab plus Clb versus Clb alone in patients with CLL and preexisting medical conditions…
  6. Genetech's obinutuzumab gets FDA Priority Review for chronic lymphocytic leukemia
  7. OncLive — "FDA Approves Lenalidomide for the Treatment of Mantle Cell Lymphoma"
  8. Marketwatch – "TG Therapeutics, Inc. Announces Presentation of Interim Results from Its Phase I/II Clinical Trial of Single Agent Ublituximab…"
  9. Daily Finance – "Spectrum Pharmaceuticals Announces Positive Data from the BELIEF Trial…"
  10. ASCO Meeting Library – "Phase Ib study combining ibrutinib with R-CHOP…"
  11. ASCO Meeting Library – "Phase III study of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) versus …"

July 2013