Prognosis For Multiple Myeloma Patients With Chromosomal Abnormality t(4;14) Remains Poor
Results of a recent French study show that multiple myeloma patients with the chromosomal abnormality t(4;14) have a high response rate after stem cell transplantation, but continue to have poor overall survival and short remission times.
Compared to conventional chemotherapy, stem cell transplantation helped the patients with t(4;14) achieve higher-quality responses. However, most patients continued to experience quick and aggressive relapses after stem cell transplantation.
The study authors indicated the need for investigation into consolidation and maintenance strategies that would slow down the rapidity and severity of relapses after remission.
Approximately 15 percent of multiple myeloma patients have the t(4;14) abnormality, a translocation of a region of chromosome 4 to chromosome 14. This abnormality is associated with poor overall survival in myeloma patients.
The chromosomal condition is also evident in a large number of patients with multiple myeloma precursor diseases, but according to Dr. S. Vincent Rajkumar, Professor of Medicine at Mayo Clinic in Rochester, Minnesota, “There is no data that patients with t(4;14) [precursor diseases] have a higher risk of progression to myeloma.”
To evaluate the prognosis of t(4;14) patients, researchers studied 102 myeloma patients with t(4;14). The median age of the patients included in the study was 56 years. Seventy-six patients had symptomatic myeloma, and 26 had a symptom-free precursor of myeloma.
Fifty-six of the 76 patients with symptomatic myeloma received high-dose melphalan with stem cell transplantation after three to four months of less intensive initial treatment. Of the 46 patients who did not undergo stem cell transplantation, 26 received conventional chemotherapy.
Ninety-three percent of the patients who received a stem cell transplant responded to the treatment, with 66 percent achieving either a complete response or a very good partial response.
Of the patients who received conventional chemotherapy, 60 percent of patients responded, with 8 percent achieving a very good partial response. None of the patients experienced a complete response.
The median progression-free survival for stem cell transplantation and conventional chemotherapy patients was 12 months and 11 months, respectively.
Within a 36-month median follow-up period, 64 patients relapsed (41 patients after stem cell transplantation and 23 after conventional chemotherapy). Thirty-seven percent of relapsed patients experienced aggressive features, such as acute kidney failure, high calcium levels in the blood, tumors outside the bone marrow, and fluid build-up around the lungs.
All relapsed patients received a rescue treatment. The rescue treatment succeeded in 51 percent of patients who relapsed after stem cell transplantation. Seventy-six percent of patients responded to a Velcade (bortezomib)-based rescue treatment, compared to 31 percent of patients who received thalidomide (Thalomid) or Revlimid (lenalidomide). Patients who received Velcade achieved a median progression-free survival of 6.9 months, compared to 3.2 months for patients who received thalidomide or Revlimid.
However, the researchers did not observe any difference in effectiveness between Velcade and thalidomide or Revlimid for patients who received conventional chemotherapy; a 26 percent response rate and a median progression-free survival of 6.5 months occurred for these patients receiving any of the rescue treatments.
The median overall survival was 31 months for patients who received a stem cell transplant, compared to 26 months for patients who received conventional chemotherapy. The median progression-free survival advantage that the researchers observed for stem cell transplant patients who received Velcade as rescue treatment compared to patients who received thalidomide or Revlimid did not translate into a significant overall survival advantage.
To improve the prognosis for patients with t(4;14), Dr. Rajkumar, who was not involved in the study, suggested focusing research on initial therapy. “Data from the University of Arkansas for Medical Sciences shows that with aggressive Velcade-based initial therapy, transplant, and then Velcade-based maintenance, survival of [patients with] t(4;14) can be similar to [those with] standard-risk myeloma,” Dr. Rajkumar told The Myeloma Beacon.
“Other studies do not show such a dramatic improvement, but do show a benefit with Velcade-based initial therapy,” he added.
For more information, please see the article in Leukemia and Lymphoma (abstract).
Related Articles:
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
- Revlimid, Velcade, and Dexamethasone, Followed By Stem Cell Transplantation, Yields Deep Responses And Considerable Overall Survival In Newly Diagnosed Multiple Myeloma
- Sustained Complete Response To Initial Treatment Associated With Substantial Survival Benefit In Multiple Myeloma
- Adding Clarithromycin To Velcade-Based Myeloma Treatment Regimen Fails To Increase Efficacy While Markedly Increasing Side Effects
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
It is true that Arkansas, uses a Gene Expression Profiling (GEP) aspiration when collecting bone marrow biopsies in their diagnostic regimen, no longer considers these chromosome deletions high risk Myeloma cases. They seem to be having more luck in getting their Myeloma tamed for longer periods of time and similarly to the low risk cases.
The article states regarding GEP: "It also enables doctors to classify a patient’s multiple myeloma based on its genomic expression profile and not just a few chromosomal abnormalities, many of which have lost their prognostic relevance in recent years (ie, del 13 and t[4;14])." - http://www.hemonctoday.com/articlePrint.aspx?type=print&rID=78250
Lori, does the outcome depend on the treatment though? I know UAMS is much more aggressive. So is their outcome more positive as a result of this?
Hanna, UAMS "tailors" the treatment for MM patients there. Of course most get this or that, but when they have someone with the GEP markers of concern they treat them at the outset with MORE. Whatever that MORE is. It could be different chemo drugs, combinations, higher doses, more rounds. It has not yet been accepted that "tailoring" a MMer's treatment makes any difference. Except that LR's numbers are continuing to impress. From a layperson's point of view, the idea that people can have different presentations of MM and yet all get the exact same treatment from a particular doctor or facility, doesn't make sense to me. But then that is what studies are for. To meat that out and determine whether the common sense theory has legs or not. So long answer short, yes the treatment matters in being able to give MMer's with chromosome deletion an opportunity to be successful.
For instance when Dave was diagnosed, the general oncologist just happened to have two newly diagnosed MM patients. Dave and another guy. The other guy had the chromosome deletion and the doctor mentioned "it" (Thalidomide/Dex) was doing NOTHING, not touching it at all. While Dave enjoyed VGPR within 30 days. That would very simply indicate to me that you would have to tailor the treatment. Would you agree?
And yes, UAMS is considered one of the more aggressive in its treatment, and some of the doctors there won't give up, which is both good and bad. Sometimes, you know, you just need to go home and be with your family. It's tough. Having said that though, I met some who were given no more options, who came to UAMS and walked out a few months later happy they came. And of course some who didn't have a good outcome.
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