7 Leukemia and Lymphoma Discoveries from ASCO 2016

Leukemia, Lymphoma and Scientific Discoveries
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Every year at the meeting of the American Society of Clinical Oncology (ASCO), researchers, patient groups and doctors who treat cancer converge share and take in the latest discoveries, continuing the work of plotting a course for the future.

There will be an estimated 81,080 new cases of lymphoma in the United States in 2016. Hodgkin lymphoma will account for about 8,500 of them, and non-Hodgkin lymphoma, the remaining 72,580.

A glimpse of this year's blood cancer-related topics follows:

1. Importance of Vitamin D Levels in Blood Cancer

Today there is greater appreciation for the importance of vitamin D, aside from strong bones. Vitamin D deficiency has been linked to muscle aches, poor strength, and even symptoms of depression. But what is the nature of the relationship between vitamin D levels and lymphoma?

In the leukemia and lymphoma community, some experts theorized that vitamin D, also known as the sunshine vitamin, may help certain cancer therapies to do their job. But does correcting the vitamin deficiency improve outcomes, as one might think? It hasn’t been an easy question to answer, thus far, and scientists are still trying to understand the effect of vitamin D as it relates to particular anti-cancer therapies.

Studies have shown a link between vitamin D deficiency and a worse prognosis in various types of blood cancer, including chronic lymphocytic leukemia (CLL), and diffuse large B cell lymphoma (DLBCL)—the most common type of non-Hodgkin lymphoma.

This year at ASCO, another B cell lymphoma was added to the list of cancers for which vitamin D has been studied—follicular lymphoma. In particular, the investigators wondered whether the supposed benefits of vitamin D depended on the type of anti-cancer therapy received by patients with follicular lymphoma.

Vitamin D insufficiency has been shown to track with worse outcomes in patients with follicular lymphoma (FL) treated with chemotherapy and an anti-CD20 monoclonal antibody—examples of which are rituximab (Rituxan) and obinutuzumab (Gazyva). The group presenting at ASCO wondered whether that finding of vitamin D deficiency means worse outcomes would hold true in all FL patients, no matter what treatment type they received.

In their study, vitamin D deficiency was defined as serum total 25(OH)D less than 20 ng/mL determined within 120 days of diagnosis. They followed a group of 659 patients with FL who entered their study from 2002-2012. Now, different folks with FL are known to have different prognoses—no matter what their vitamin D levels may be—so they tried to adjust for these things.

Here are some of their findings:

  • The mean age at diagnosis was 60 years (range 23-93)
  • Some 34 percent of patients with FL had vitamin D insufficiency.
  • Vitamin D insufficiency was associated with worse overall survival, and in the few cases where it could be determined—lymphoma-specific survival—and this seemed to be true no matter what treatment was received.
  • Vitamin D insufficiency was also associated with more problematic events—as measured in ‘event-free survival’ in all patients and in patients specifically treated with immune therapy such as rituximab.

    The bottom line seems to be that it is important to have adequate levels of vitamin D, and that more studies are needed to better understand the relationship between vitamin D levels and outcomes for the various types of lymphoma.

    2. Life After DLBCL—Which Cancers Are Most Likely?

    Diffuse large B-cell lymphoma, or DLBCL, is the most common lymphoma. A new era of treatment for DLBCL was ushered in since rituximab became standard in 2001, and a group of researchers presenting at ASCO wanted to know how this is fact is reshaping the subsequent diseases that surface in survivors, in terms of which second primary malignancies are most common.

    • Hodgkin lymphoma: They found that the risk of HL was elevated in both treatment eras – before and after 2001 – but that risk decreased somewhat after-rituximab
    • Acute myeloid/monocytic leukemia: The risk of acute myeloid/monocytic leukemia (AML) nearly doubled after the introduction of rituximab.
    • Thyroid cancer: Thyroid cancer after DLBCL was rare pre-rituximab, but increased substantially after rituximab was introduced.
    • Risks for lung and liver cancer were elevated, while risks for colorectal and breast cancer decreased, in the post-rituximab era.

    3. PFS, OS (and CD15)... What Does It All Mean in Hodgkin lymphoma?

    CD15—known to organic chemistry buffs as 3-fucosyl-N-acetyl-lactosamine—is a marker that has been studied in patients with head and neck and colorectal cancers. CD15 is a compound that, in some cases, shows up on the outside of malignant white blood cell-lymphocytes. It is thought to be involved in how the immune system reacts to malignant lymphocytes. CD15 is found in 66 percent of patients with Hodgkin lymphoma (HL) and 20 percent of those with non-Hodgkin's lymphoma, according to the group’s published work.

    A group of researchers wanted to see if CD15 could be used to indicate prognosis in Hodgkin’s lymphoma, and they presented their findings at this year’s ASCO meeting. They found that progression-free survival—the time survivors spent without any progression of their cancer—was shorter for people whose lymphoma lacked the CD15 marker compared to those who had it: 4 years versus 36 years.

    That seems like a big difference, and it is; however, this case gives a wonderful example of how progression free survival (PFS) and overall survival (OS) can indicate very different things:

    In this case, one group had cancer that returned roughly within the first year, and in the other, cancer recurrence more commonly took place decades later, if at all. But overall survival was not different between the groups... Why? Because, when there was progression of the cancer in the CD15- folks, doctors had an effective backup treatment to use—this is referred to as ‘salvage therapy’—which, once administered, gave these patients a survival rate akin to the first group.

    4. Mantle Cell Lymphoma: What’s the Prognosis?

    Mantle cell lymphoma (MCL) is a group of aggressive lymphomas that respond differently to treatment – that is, some people have better outcomes after treatment for MCL than others. There are many different ways doctors and researchers have tried to measure and predict the prognosis for a person with MCL.

    A group of researchers at this year’s ASCO meeting described their experience implementing a new test that measures something called the “proliferation signature,” using molecules from routinely processed lab biopsies.

    Proliferation signature refers to the presence of those genes linked to the aggressive cancerous properties of the cell—such as speedy cell division, for example—genes that, when they are turned on, are linked to spread, aggressiveness and decreased survival.

    The group was successful in their efforts in that they were able to use the proliferation signature testing system to sort out people with MCL into differing risk groups with significantly different overall survival—all based on the biopsy specimens. The newly developed test is called the MCL55 assay.

    5. CAR T-cells for Relapsed/Refractory B-cell malignancies

    Also called adoptive cell transfer, CAR T-cell therapy is a new therapy which has garnered a lot of media attention. It involves engineering the patients’ own immune cells to recognize and attack their tumor cells. Although this type of therapy is currently experimental and has been restricted to a few small clinical trials so far, it has shown some remarkable responses in patients with advanced cancer.

    As such, people are looking into the possibility of “mass producing,” if you will, CAR T cell therapies, to the extent possible. A group is testing the very same CAR T-cell therapy idea used in a National Cancer Institute trial (CARCD28/CD3z anti-CD19 CAR T cells) in patients with relapsed/refractory B cell malignancies. Their product, KTE-C19, is essentially the same combination as in the NCI trial, but this time it is centrally manufactured in a streamlined 6 to 8 day process.

    At ASCO they reported that, as of Jan 15, 2016, some 7 patients were dosed with KTE-C19. One patient experienced a dose-limiting toxicity—something called cytokine release syndrome (CRS) and also neurotoxicity (NT).

    However, no additional KTE-C19 related adverse events were observed after 1 month from dosing. And 5 of patients had an objective response while 4 had a complete response. The central manufacturing process and the KTE-C19 regimen evaluated was deemed safe and feasible for further study.

    6. Primary Breast Lymphoma

    Primary breast lymphoma—meaning lymphoma that starts in the breast—is a rare cancer that involves the lymph nodes of the breast only, without any evidence of disease elsewhere in the body. It is a non-Hodgkin’s lymphoma (NHL).

    A group presenting at ASCO evaluated the trends of incidence and prognosis in this malignancy from 1983 to 2012.

    • The rate increased with advancing age from 50 years old to above 80 years old.
    • The incidence rate almost doubled from during 1983-92 to 2003-12.
    • The median overall survival (OS) was better than for all NHL.
    • Histological type—what the pathologists glean about the cancer from tissue samples viewed and tested microscopically—didn’t affect the prognosis in primary breast lymphoma, in unlike in NHL.

    The authors concluded that primary breast lymphoma is on the rise in the United States.

    7. Latest U.S. Stats on NK/T Cell Lymphoma

    If you should ever start reading about NK/T cell lymphoma, the topic always seems to quickly turn to Asia and South America, where this malignancy is apparently more common, but things are changing.

    Little was known about NK/T Cell lymphoma in a US population, so a group of researchers decided to “put America first” by using the National Cancer Data Base (NCDB) to examine cases from the years 1998-2012 in the United States, and a few highlights of their findings appear below:

    • Of the 563,833 U.S. patients diagnosed with NHL, 1,398 (0.2 percent) had NK/T cell lymphoma.
    • The median age at diagnosis was 53 years (range, 18 – 90+) and 66 percent were males.
    • There did not seem to be a difference in overall survival (OS) based on era of diagnosis (diagnosed in 2002 or earlier vs. 2003-2008 vs. 2009 or later), but survival did seem to improve for patients who received stem cell transplants.

    Thus, NK/T cell lymphoma is rare type of non-Hodgkin lymphoma, or NHL.

    It is highly associated with the Epstein-Barr virus (EBV)—the same virus that causes infectious mononucleosis, or mono. EBV is a risk factor for certain kinds of lymphoma, but it would be incorrect to say that EBV is the cause of these cases of lymphoma. According to the American Cancer Society, EBV infection doesn’t cause serious problems in most people.


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    2. J Clin Oncol 34, 2016 (suppl; abstr e19067)

    3. J Clin Oncol 34, 2016 (suppl; abstr e19038)

    4. J Clin Oncol 34, 2016 (suppl; abstr 7543)

    5. J Clin Oncol 34, 2016 (suppl; abstr e19010)

    6. J Clin Oncol 34, 2016 (suppl; abstr 7510)

    7. J Clin Oncol 34, 2016 (suppl; abstr e19026)

    8. J Clin Oncol 34, 2016 (suppl; abstr e19038)