A happy Sunday to you, myeloma world.

We hope you have been having a pleasant weekend. We've been looking over some of the new multiple myeloma research published in the past few days, and there are two studies we thought we would discuss with you in today's Myeloma Morning ^[1].

The first is a case report involving a myeloma patient who has been in remission for more than 15 years. This remission, it seems, may be an unexpected “side effect” of radiation treatment the patient received.

The second study we'll be summarizing is focused on an important question: Are the patients who take part in multiple myeloma clinical trials similar to multiple myeloma patients in general? The answer, say the authors of the new study, is “No.”

A Case Of The Abscopal Effect In Multiple Myeloma

Our first article today is related to a rare, but potentially very positive, side effect of radiation therapy. It is known as the “abscopal effect.”

The abscopal effect occurs when radiation intended to treat a cancer tumor in a very specific location of the body instead has a much broader effect. The more widespread effect of the radiation causes regression, or even elimination, of the cancer throughout the patient's body.

This “side effect” of radiation therapy is very rare. However, it has been reported to occur in a number of different cancers, including cancer of the kidney, skin cancer, and certain types of lymphoma. It also has been the subject of serious research by, for example, scientists at Memorial Sloan-Kettering Cancer Center in New York City (full text ^[2] of related article in the New England Journal of Medicine).

It is believed that the abscopal effect is a result of an immune system reaction to radiation therapy. The body perceives the radiation as a threat; it creates an immune response to protect the body; and that immune response attacks the cancer cells in the body.

In a case report published several days ago, three physicians in Chicago describe a multiple myeloma patient who they believe has had a long-term remission as a result of the abscopal effect (abstract ^[3]).

The patient was diagnosed with IgG lambda multiple myeloma in 1996. She was 49 years old at the time and had an M-spike over 3.0 g/dL. She initially was treated with melphalan and prednisone, then underwent additional treatment with several other chemotherapy regimens before having an autologous stem cell transplant in February 1998.

In November, 1998, the patient's multiple myeloma began to relapse, so she started treatment with interferon and dexamethasone, and then had treatment for 3 or 4 months with thalidomide and dexamethasone starting in May, 1999.

Later in 1999, as her M-spike started to rise again and treatment options were limited, the patient developed plasmacytomas on her thighs and in her stomach area. Each of these were treated with multiple courses of radiation to control the tumors and offer some pain relief.

In early 2000, more than half a year since her last drug treatment for multiple myeloma, the patient's IgG level started to drop, indicating that her M-spike also was dropping. Her IgG level continued to drop and, ever since the middle of 2000, it has been in the normal range.

The patient is still alive 20 years later and has not needed any further treatment for her multiple myeloma.

Based on their review of the patient's treatment history and how her body responded to the radiation she received, the authors of the case report conclude:

“The constellation of our findings points towards an abscopal effect due to a global immunogenic effect of radiation, similar to that seen in solid tumours. This makes our case the first reported in the literature of the abscopal effect in multiple myeloma and one of the very few, to the best of our knowledge, of long-term survival (20 years to date) and possible cure.”

(Note: An earlier version of this article reported that the patient in the case report was 69 when she was diagnosed. We have since learned that the patient is currently 69 years old.)

How Representative Are The Patients In Multiple Myeloma Clinical Trials?

The second study we look at today is by a trio of authors based at different U.S. cancer centers. They investigate whether the multiple myeloma patients who participate in clinical trials in the United States are similar to – or different from – multiple myeloma patients in general (abstract ^[4]).

For their investigation, the researchers identified all multiple myeloma clinical trials carried out in the United States which had their results published between 2007 and 2014. The authors reviewed the published results of the trials and recorded information that was reported about the age, gender, race, and disease stage of the patients in the trials.

Next, the authors turned to data from the U.S. National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database of cancer patient characteristics. The data allowed the researchers to determine what age and other characteristics the patients in the myeloma trials would have had if they had been selected at random from all myeloma patients.

What the authors found is that “minorities, older individuals, and persons with more advanced disease are underrepresented in multiple myeloma trials.” This disparity, the authors argue, could compromise the ability of researchers to draw broader conclusions based on the results of their trials. They write that

“there is a clear need for development of age-specific clinical trials, given that the vast majority of multiple myeloma patients are >65 years at the time of diagnosis. Such trials should have less restrictive eligibility criteria and test simpler therapeutic interventions that are relevant for older patients and patients with comorbidities.”

The authors also found that data on minority participation in multiple myeloma trials was not reported in most of the publications they found, despite the fact that information on minority status is collected from participants during trials. They recommend that such information be reported regularly in the future, and they also

An earlier version of this study was presented during the most recent American Society of Hematology meeting (abstract ^[5], slide deck ^[6]).

New Myeloma-Related Research Articles

1. Abid, M. B. et al., “Bortezomib-related neuropathy masking CNS relapse in multiple myeloma; a unique case report and review of the literature” in Cancer Biology & Therapy, April 22, 2016 (abstract ^[7])
2. Costa, L. J., Hari, P. N. & Kumar, S. K., “Differences between unselected patients and participants in multiple myeloma clinical trials in US: a threat to external validity” in Leukemia & Lymphoma, April 22, 2016 (abstract ^[4])
3. Khurana, U. et al., “Oligosecretory multiple myeloma: a case report” in Blood Research, March 25, 2016 (full text ^[8])
4. Lee, J. W. & Lee, J. E., “Local radiotherapy for palliation in multiple myeloma patients with symptomatic bone lesions” in Blood Research, March 30, 2016 (full text ^[9])
5. Sergentanis, T. N. et al., “Cytogenetics and survival of multiple myeloma: isolated and combined effects” in Clinical Lymphoma, Myeloma & Leukemia, March 29, 2016 (abstract ^[10])
6. Suen, H. et al., “Multiple myeloma causes clonal T cell immunosenescence: Identification of potential novel targets for promoting tumour immunity and implications for checkpoint blockade” in Leukemia, April 22, 2016 (abstract ^[11])