Good morning, myeloma world.

After a busy week here at Myeloma Morning Headquarters, we're pleased to report that things are a bit more relaxed today. We're not sure if it's the weekend, or the cooler, overcast weather outside. Whatever the reason, we're enjoying the somewhat slower pace.

That pace is reflected in what we'll be covering in today's edition of Myeloma Morning. We'll be discussing just three new myeloma research articles.

The first article is a discussion of how to treat relapsed multiple myeloma, co-authored by Dr. Pieter Sonneveld, a leading myeloma researcher based in the Netherlands.

The second article is by a group of Swedish researchers, who investigate the survival of multiple myeloma patients who have been diagnosed with a secondary cancer.

Finally, we look briefly at a Dutch study reporting on the use of weekly Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone in myeloma patients who have had one prior treatment.

Treatment of Relapsed Multiple Myeloma

Let's look first at the article written by Dr. Sonneveld together with Dr. Annemiek Broijl, both of the Erasmus University Medical Center in the Netherlands (full text).

This article is not a presentation of new research results. Instead, it is a summary of the approach Drs. Sonneveld and Broijl recommend for the treatment of relapsed multiple myeloma. The full text of the article is available online at no charge, and, although it can be technical, myeloma patients and caregivers should find it useful for at least two reasons.

First, it discusses the definition of relapse, and also when treatment should be changed or restarted during the relapse process. The authors note, for example, that “In the case of relapse presenting with new or worse 'CRAB' symptoms, immediate treatment is mandatory.” They also explain that relapse can be either symptomatic or “biochemical,” which is relapse with no symptoms, but increasing M-spike or serum free light chain levels. After defining what biochemical relapse is, they explain which patients experiencing a biochemical relapse should restart treatment (or have their treatment changed):

“In the presence of high-risk factors, such as aggressive disease at diagnosis, a short treatment-free interval with a suboptimal response to the previous treatment line, imminent risk for organ dysfunction such as previous light chain-induced renal impairment, aggressive bone lesions or unfavorable cytogenetics t(4;14) or del17p, treatment should be initiated at the stage of biochemical relapse before serious symptomatic disease develops.”

Second, Drs. Sonneveld and Broijl outline factors to consider when deciding what treatment a myeloma patient should receive at relapse, and also share specific recommendations for certain categories of relapsing patients based, for example, on their previous treatment history. (See this figure for a summary of factors to consider, and this figure for treatment suggestions.)

Now, the treatment recommendations the authors make are better suited to myeloma patients outside the United States, as they do not fully take into account the treatments now available in the United States for use at relapse. Nevertheless, the authors' discussion of factors to consider is a useful introduction to how to think about relapsed-related treatment decisions.

Secondary Cancers

It's been a little more than five years since the issue of secondary cancers exploded onto main stage in myeloma world. The possible connection between, in particular, Revlimid and increased rates of “second primary malignancies” was a constant topic of discussion in late 2010 and early 2011.

Since then, a consensus has developed that Revlimid does tend to increase the rate of secondary cancers in myeloma patients, but this occurs mainly when the drug is taken at the same time as orally administered melphalan (see related Beacon news article).

Secondary cancers, however, have been occurring in multiple myeloma patients since long before the introduction of Revlimid, and Revlimid is not the only myeloma-related treatment that may increase the risk of such malignancies.

In the second paper we'll look at today, a group of Swedish researchers investigate what the survival of multiple myeloma patients has been when they have been diagnosed with a second cancer (full text). To address this issue, the researchers work with a dataset with information on all multiple myeloma patients diagnosed in Sweden between January 1, 1958 and December 31, 2011.

The study authors find that, across the entire period covered by their dataset, myeloma patients diagnosed with a second cancer lived a median of 1.1 years after the diagnosis of their second cancer.

The 1.1-year survival was about 2 years less than what would have been expected had the myeloma patients not been diagnosed with the second cancer, based on the survival of similar myeloma patients not diagnosed with a second cancer.

Survival after a second cancer diagnosis did seem to go up, however, in more recent years. Data presented by the authors suggests that, for the period 2001-2011, diagnosis after a secondary cancer diagnosis was about 2.2 years, versus about 1 year in the 1958-2000 period.

Unfortunately, one form of secondary cancer that can strike myeloma patients is particularly difficult to treat. This is secondary cancer that takes the form of either acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).

The Swedish researchers found that myeloma patients who developed AML or MDS in the 1958-2011 period had an overall survival of less than 3 months after the second cancer was diagnosed. MD Anderson researchers also have estimated the survival of these myeloma patients to be low – about 6 months – using data for patients seen at their treatment center between 1993 and 2011 (abstract; full text at PubMed).

Once-Weekly Velcade, Revlimid, And Dexamethasone As Second Therapy

We close our review of new myeloma-related research today with a quick mention of an article reporting results from a clinical trial. In particular, Dutch researchers have published results of a Phase 1/2 trial they conducted. The trial, known as HOVON 86, tested once-weekly intravenous Velcade (bortezomib) combined with Revlimid and dexamethasone – and followed by Revlimid maintenance – in myeloma patients who have had one prior therapy (full text).

We won't spend too much time on this study because the patient population is somewhat unique. Specifically, patients in the study could not have been previously treated with either Velcade or Revlimid. Given how frequently these two drugs are now used as part of initial therapy given to newly diagnsoed myeloma patients, the results of this trial are not likely to apply to many patients in the future.

Thus, we will just note that the overall response rate in the trial – at the dose used in Phase 2 of the study – was 89 percent. Median progression-free survival was 19 months, and median overall survival was 42 months.

New Myeloma-Related Research Articles

1. Broijl, A. et al., “Phase I/II trial of weekly bortezomib with lenalidomide and dexamethasone in first relapse or primary refractory myeloma” in Haematologica, March 31, 2016 (full text)
2. Jonsdottir, G. et al., “Survival in multiple myeloma patients who develop second malignancies: a population-based cohort study” in Haematologica, March 31, 2016 (full text)
3. Snee, M. J.et al., “Collaborative control of cell cycle progression by the RNA exonuclease Dis3 and Ras is conserved across species” in Genetics, March 30, 2016 (full text)
4. Sonneveld, P. et al., “Treatment of relapsed and refractory multiple myeloma” in Haematologica, March 31, 2016 (full text)
5. Wale, A. et al., “Frequency, distribution and clinical management of incidental findings and extramedullary plasmacytomas in whole body diffusion weighted magnetic resonance imaging in patients with multiple myeloma” in Haematologica, March 31, 2016 (full text)