I get questions from smoldering myeloma patients often these days. They ask, “Should I join (pick a study) and start treating my smoldering myeloma early?”
Because that’s the big new thing these days–identifying which smoldering myeloma patients are most likely to make the jump to active myeloma–and then trying to find ways to slow down the progression.
I have shared my opinion about this here before; that I don’t think it is a good idea to expose one’s myeloma to novel therapy agents until they absolutely need to.
But there is new data emerging that might prove there can be an overall survival benefit to attacking smoldering myeloma early in an attempt to keep it from progressing.
Specifically, there is an ongoing Spanish study,
Smoldering Multiple Myeloma (SMM) At High-Risk of Progression to Symptomatic Disease: A Phase III, Randomized, Multicenter Trial Based On Lenalidomide-Dexamethasone (Len-Dex) As Induction Therapy Followed by Maintenance Therapy with Len Alone Vs No Treatment
which concludes that:
“high-risk SMM patients, delayed treatment resulted in early progression to symptomatic disease (median 25 months), while Len-dex as induction followed by Len as maintenance significantly prolonged the TTP (HR: 6·2), with a trend to improve the overall survival.”
CLICK HERE to access the abstract, which was presented at last year’s ASH.
There are a large number of similar studies currently enrolling patients here in the states. That’s why I get so many questions on the topic.
The key to all of this is being able to identify smoldering myeloma patients who are at highest risk of progressing.
News-Medical.net ran this report last week about a new way to do just that:
By Lynda Williams
Published on July 18, 2012
Smoldering multiple myeloma (SMM) patients with bone marrow plasma cell (BMPC) involvement should be treated immediately, say Italian researchers who found these patients are at greatest risk for symptomatic disease.
BMPC of 60% or greater determined using bone marrow aspiration (BMA) was associated with a significant 5.6-fold increased risk for progression to symptomatic multiple myeloma (sy-MM) within 2 years compared with a lower BMPC proportion, report Giuseppe Cimino (“Sapienza” University Polo Pontino, Rome) and co-workers in Cancer.
The team followed up 397 patients with SMM attending 12 specialist centers for a median of 54 months, during which time 37.5% of patients progressed to sy-MM. Overall, 43% of patients survived 10 years, 38% 15 years, and 24% survived 20 years; the cumulative incidence of progression at these time points was 45%, 55%, and 75%, respectively.
Initial analysis showed that progression to sy-MM at 120 months was significantly predicted by hemoglobin level above 12.5 g/dL (65 vs 50% for 10.5‑12.5 g/dL), monoclonal component above 2.5 g/dL (65 vs 35% for <2.5 g/dL), and BMCP greater than 60% on BMAA (100% vs 50 and 60% for BMCP <15% and 15‑30%, respectively).
In multivariate analysis, however, only BMPC greater than 60% significantly predicted risk for progression.
When grouped by BMPC, 39% of patients had a proportion below 15%, 58.5% had a proportion of 15‑59%, and 2.5% had a BMPC of 60% or above. The rate of progression to sy-MM significantly differed between the groups, at 35.0%, 38.6%, and 80.0%, respectively.
Of note, patients with a BMPC of 60% or above had significantly lower hemoglobin levels, higher serum monoclonal components, and a higher rate of severe clinical manifestation on progression than those with lower BMPC. However, BMPC did not significantly predict survival, the researchers report.
Cimino et al highlight that BMA results for BMPC significantly differed from bone marrow biopsy (BMB) findings, with a median value of 19% and 25%, respectively, and the distribution of patients in the three BMPC groups therefore significantly differed.
“The present data show that SMM patients with ≥60% BMPC rate at diagnosis presented a very rapid progression to sy-MM, which in the majority of cases were also characterized by more severe clinical manifestations… suggesting that these SMM patients should probably be candidates for treatment already at diagnosis,” the team concludes.
“Furthermore, with respect to the identification of these very high-risk SMM patients, in our study, BMPC of 60% or higher detected by BMA was more prognostic for rapid progression to syMM compared with BMB. This finding strongly suggests that BMB is not helpful in the assessment of patients with SMM,” they conclude.
If I were a smoldering patient with a large percentage of plasma cells in my bone marrow, I might strongly consider participating in one of these clinical trials.
Feel good and keep smiling! Pat