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Vitamin D prognostic for Hodgkin’s disease?

Elvira Manzano
27 Jul 2018

Vitamin D deficiency in patients with Hodgkin’s disease may be a tell-tale sign of what is forbidding to come: poor progression-free survival (PFS) and overall survival (OS), according to an analysis of three studies.

“It was surprising to see such a large effect on PFS and OS. This is the first time that, in a very large study, vitamin D levels were shown to be prognostic for Hodgkin lymphoma,” said Dr Stefano Luminari from the University of Modena and Reggio Emilia, in Modena, Italy, co-moderator at the EHA session. “Now, the question is can we revert the prognostic features by supplementing these patients with vitamin D therapy?”

Of 351 patients in the studies, 175 were vitamin D deficient, 83 had insufficient vitamin D levels, and 93 had sufficient levels based on current food and nutrition guidelines by the Food Nutrition Board of the Institute of Medicine, US. Serum level of <30 nmol/L was defined as vitamin D deficient, 30 to 50 nmol/L as insufficient, and 50 nmol/L or higher as sufficient. Of the total number of patients, 233 were relapse-free and 118 relapsed. [EHA 2018, abstract S111]

Patients who experienced relapse or progression had significantly lower median baseline vitamin D levels vs those who were relapse-free (21.4 vs 35.5 nmol/L) and were more likely to be deficient in vitamin D (p<0.0001).

Increased risk comes as a ‘surprise’

After adjusting for time of diagnosis, age, and sex, vitamin D deficiency was strongly associated with lower PFS (hazard ratio [HR], 2.13, 95 percent confidence interval [CI], 1.84–2.48; p<0.0001) over a median time of 156 months.

As for OS, vitamin D–deficient patients also had a significantly higher risk of death (HR, 1.82; 95 percent CI, 1.53–2.15; p<0.0001) over a median observation time of 192 months in the weighted analysis.

The increased risk was “a bit of a surprise,” said lead author Dr Sven Borchmann from the German Hodgkin Study Group and the University Hospital of Cologne in Cologne, Germany. “Looking at the hazard ratios, 2.13 for PFS and 1.82 for OS in the weighted models, these are quite high compared to other studies in solid cancers, especially that the order of magnitude of the effect is similar to the improvements that are usually deemed as practice-changing when it comes to evaluating a new intervention.”

But he was quick to explain that although directly incomparable “any intervention, for example, a new drug or a treatment modality that would show this difference in a prospective trial in Hodgkin lymphoma, would likely be quickly picked up by practitioners, given its safety, and reasonable cost-benefit ratio.”

More deaths in vitamin D deficient patients

Twenty-four patients (38 percent) who were vitamin D deficient died of Hodgkin lymphoma vs four (22 percent) in those whose level of vitamin D was insufficient, and three (18 percent) in patients who had sufficient vitamin D levels.

Of note, total deaths from all causes were higher in vitamin D deficient patients (n=63, 36 percent) than those with insufficient vitamin D levels (n=18, 22 percent) or those with sufficient levels (n= 17, 18 percent).

“The differences in OS rates appear to be mainly due to significantly more Hodgkin lymphoma-associated deaths in vitamin D deficient patients,” said Borchmann. “Of note, the lower rates of PFS and OS were independent of tumour mass and type of treatment received.”

No correlation with ESR, B-symptoms

The data analysed were from the GHSG HD7, HD8, and HD9 studies involving patients with favourable-to-advanced disease status. Their pretreatment serum samples, as well as progression or relapse, were also looked into.

Aside from PFS and OS, there were no correlations between vitamin D levels and other factors such as age, sex, clinical stage, large mediastinal mass, extranodal involvement, elevations in erythrocyte sedimentation rate (ESR), B-symptoms, or Karnofsky index score.

Vitamin D deficiency is a known predictor of poor prognoses in many cancers. But there have been no data on pretreatment vitamin D levels or if vitamin D levels correlate with patient characteristics and outcomes in Hodgkin lymphoma, Borchmann said. “Our study showed quite a strong effect, and given that Hodgkin lymphoma is so intertwined with its microenvironment, consisting of many different immune cell subtypes, this might point to a specific role vitamin D deficiency has in maintaining a supportive microenvironment for Hodgkin lymphoma to survive.”

Whether their finding holds true is subject to more studies. Prospective studies and laboratory experiments looking at the effects of active forms of vitamin D on cell proliferation of Hodgkin’s lymphoma and how it interacts with various immune effector cells are warranted, Borchmann concluded.

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