Treatment Advances for Leukemia and Lymphoma

Takeaways From Blood Cancer Research

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Each year the American Society of Hematology (ASH) holds a conference presenting the latest research on medicines and other treatment advances. Medicines that are discussed at this meeting are in all different phases of clinical development. In other words, some of them are current medications, tried and true, already approved and in use, and others are truly research medications, meaning we don’t know much about them yet.

Take rituximab, for example. In 2016, Rituximab was considered an “old stand-by” medication that has been used for years to treat many different types of non-Hodgkin lymphoma. Older, more established medicines can still make waves at one of these conferences, for instance, when a new use is discovered.

Some drugs discussed at ASH are just in the first stage of development—that is, the discoveries being shared are very preliminary. Often, these studies are described “phase-I studies.” Phase I refers to clinical trials that test a new drug or treatment in a small group of people—for the first time ever— to see if it works, to find a safe dosage range, and to identify side effects. Phase I trials are like seeds: you might eventually get an award-winning plant or fruit that you can show off at the state fair, but you can also get failure to sprout or a plant that doesn't bear much fruit.

Research on DLBCL

Diffuse large B-cell lymphoma, or DLBCL, is a fast growing lymphoma.

It’s the most common type of lymphoma in adults, and it comes from the B-lymphocytes—white blood cells that lead to antibody production in the immune system. Different people have different kinds of DLBCL and researchers are investigating newer options for patients with DLBCL.

Rituximab Plus CHOP or DA-EPOCH-Rituximab

One phase III study had 524 patients registered (262 on each treatment arm) between May 2005 and May 2013. This study compared R-CHOP treatment and DA-EPOCH-R treatment, a more chemotherapy-intensive treatment, in hopes of extending survival in patients with recently diagnosed stage II or higher DLBCL.

Participants were at least 18 years old and HIV-negative. So far, overall, DA-EPOCH-R was associated with more toxicity and side effects, and there was no difference between the groups in terms the treatment benefits studied. Still, investigators are looking to see about particular subgroups of people with DLBCL and whether or not benefit with DA-EPOCH-R will be shown for subgroups. Analyses are ongoing.

Obinutuzumab Plus CHOP or Rituximab Plus CHOP

This was another phase III study with 1,418 participants evaluated the efficacy and safety of obinutuzumab vs. rituximab plus CHOP in patients with DLBCL. Participants were 18 years old or older and previously untreated for DLBCL. Overall, there was no marked difference between the two groups in terms of survival benefits, and more adverse events were reported for patients in the obinutuzumab-CHOP than rituximab-CHOP group. Overall, mortality rates were higher and withdrawal from treatment more common in the obinutuzumab -CHOP arm.

However, the investigators plan to look at subgroups with DLBCL to try and find any benefits or risks that were not reflected in the group as a whole.

Lenalidomide in Patients with Relapsed DLBCL

People who are not eligible for a bone marrow transplant or are experiencing relapse after having a marrow transplant have a low likelihood of cure, so one particular research group looked into using a medication to prolong survival in these patients.

They found that the agent lenalidomide is a suitable candidate since it is an oral drug, active against DLBCL that can be taken for years with an acceptable toxicity profile.

The study demonstrated that older patients with different kinds of DLBCL benefited from lenalidomide maintenance therapy with improved survival. Maintenance therapy refers to treatment of cancer with medication, usually following an initial round of treatment.

Research on Follicular Lymphoma

Follicular lymphoma is the most common type of indolent—that is, slow growing—lymphoma. While obinutuzumab did not seem to offer any obvious advantages yet in the DLBCL study mentioned above, that was not the case for obinutuzumab in follicular lymphoma.

Obinutuzumab-Based Therapy Prolongs Progression-Free Survival in Patients With Previously Untreated Follicular Lymphoma

The GALLIUM trial was an international phase 3 study comparing the efficacy and safety of rituximab or obinutuzumab with chemotherapy followed by maintenance as first-line treatment for indolent non-Hodgkin lymphoma.

In patients with previously untreated follicular lymphoma, the obinutuzumab-based chemotherapy regimen and maintenance program resulted in a clinically meaningful improvement in survival without the disease progressing —a 34 percent reduction in the risk of progression relative to rituximab-based therapy. Obinutuzumab had a higher frequency of some adverse events such as infusion-related reactions, low blood counts, and infections. Researchers concluded the data support obinutuzumab-based regimen becoming the new standard of care in previously untreated patients with follicular lymphoma.

Research on Hodgkin Lymphoma

There are five major types of Hodgkin lymphoma (HL) that a person may be diagnosed with. Classical Hodgkin lymphoma is an older term used to describe a group of four common types that together comprises more than 95 percent of all cases of HL in developed countries.

Immune Checkpoint Inhibition for Relapsed Classical Hodgkin Lymphoma

Classical Hodgkin lymphoma seemed to have genetic changes that would make it susceptible to a new class of medications called immune checkpoint inhibitors, based on previous studies. So, a research group at ASH looked at 210 patients treated for refractory disease or relapsed HL to see how the checkpoint inhibitor pembrolizumab would do.

Some cancer cells produce large amounts of PD-L1, and this is something that helps them escape immune attack. Pembrolizumab can help put a stop to that. PD-1 blockade with pembrolizumab worked in groups of patients with classical HL who had been heavily pretreated with other therapies. Pembrolizumab had a high response rate even in disease that was resistant to chemotherapy. Additional results, including how long the response remained in effect were expected at the meeting.

Research on Leukemia

Supportive Therapy for Patients With AML - Eltrombopag

In patients undergoing intensive chemotherapy for acute myelogenous leukemia (AML), sometimes the platelet counts stay low after the chemotherapy, and this can lead to increased risks of bleeding, the need for many platelet transfusions, and patients can develop immune reactions to the platelets, which all serves to hinder progress.

In 2016 a group reported using eltrombopag, a medicine that prompts the body to make more platelets, in older people who were undergoing treatment for AML.

Results were preliminary—this was a phase I pilot study—but they seemed to have some success with getting people to recover more quickly from chemo so that they would not require as many platelet transfusions. There had been concern that an agent such as eltrombopag might accelerate the progression of the leukemia, in addition to potential benefits with helping the platelets recover, however, so far in this study there is no evidence of that risk being a reality.

Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

There is no standard regimen for relapsed ALL. Inotuzumab ozogamicin is an FDA-designated breakthrough therapy for patients with relapsed or refractory acute lymphoblastic leukemia (ALL). In one clinical trial, inotuzumab ozogamicin produced significant improvements over standard chemotherapy in patients with ALL refractory to, or not responding to, other therapies.

Inotuzumab ozogamicin is an investigational antibody–drug combination made up of an antibody linked to an agent that can kill cancer cells. When the drug binds to a tag called CD22 on the cancer cells, it internalizes into the cell where it causes the DNA to break, leading to cell death.

What the Research Means for You

While conferences are often geared to provide medical practitioners with the latest research, the information is often of interest to those diagnosed with the conditions, as well as their loved ones. When you visit your doctor ask about what's new in the field—being in the know can help you feel more in control of your health.

Sources:

469 Phase III Randomized Study of R-CHOP Versus DA-EPOCH-R and Molecular Analysis of Untreated Diffuse Large B-Cell Lymphoma: CALGB/Alliance 50303

474 Lenalidomide Maintenance Significantly Improves Survival Figures in Patients with Relapsed Diffuse Large B-Cell Lymphoma (rDLBCL) Who Are Not Eligible for Autologous Stem Cell Transplantation (ASCT): Final Results of a Multicentre Phase II Trial

470 Obinutuzumab or Rituximab Plus CHOP in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma: Final Results from an Open-Label, Randomized Phase 3 Study (GOYA)

1107 Pembrolizumab in Relapsed/Refractory Classical Hodgkin Lymphoma: Primary End Point Analysis of the Phase 2 Keynote-087 Study

447 A Single Arm, Phase II Study of Eltrombopag to Enhance Platelet Count Recovery in Older Patients with Acute Myeloid Leukemia Undergoing Remission Induction Therapy

6 Obinutuzumab-Based Induction and Maintenance Prolongs Progression-Free Survival (PFS) in Patients with Previously Untreated Follicular Lymphoma: Primary Results of the Randomized Phase 3 GALLIUM Study

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