Dr. Kenneth Anderson, a world-renowned myeloma spe­cialist, physician and re­searcher at Dana-Farber Cancer In­sti­tute, and Kraft Family Pro­fessor at Harvard Medical School, spoke with The Myeloma Beacon about his ap­proach to treating mul­ti­ple myeloma patients.

This article is the sec­ond part of a two-part series based on The Myeloma Beacon’s interview with Dr. Anderson.  It will cover Dr. Anderson’s thoughts on where myeloma treat­ment is headed in the com­ing years.  For more in­­for­ma­tion on Dr. Anderson’s cur­rent ap­proach to treating mul­ti­ple myeloma, please see part one ^[1] of this series.

Emerging Therapies

According to Dr. Anderson, there are sev­er­al promising agents being devel­oped to treat mul­ti­ple myeloma.

The first promising agent that he discussed was carfilzomib ^[2], a pro­te­a­some in­hib­i­tor like Velcade ^[3] (bor­tez­o­mib).  “Carfilzomib appears to be active in re­lapsed myeloma and very well tol­er­ated with very little in the way of neu­rop­athy [pain or tingling in the extremities],” Dr. Anderson ex­plained.

He was also impressed with pomalidomide ^[4]’s po­ten­tial.  Poma­lido­mide is an immuno­modu­la­tory drug like thalidomide ^[5] (Thalomid) and Revlimid ^[6] (lena­lido­mide).  “Pomalidomide, like thalido­mide and Revlimid, targets the tumor in the microenvironment, but ex­cit­ingly poma­lido­mide is active even when thalido­mide and Revlimid are not.  Poma­lido­mide is also active when Velcade is not.”

Besides these two inves­ti­ga­tional drugs, Dr. Anderson saw the most po­ten­tial in com­bi­na­tions of treat­ments.

Dr. Anderson mentioned com­bi­na­tions of Velcade and a histone deacetylase in­hib­i­tor, either Zolinza ^[7] (vorinostat) or panobinostat ^[8] (Farydak ^[9]), which have achieved re­sponses in the majority of patients who have not responded to Velcade.

He also felt that Velcade in com­bi­na­tion with the AKT in­hib­i­tor perifosine ^[10] appears to be ef­fec­tive in patients who have pre­vi­ously been treated with or did not respond to Velcade.

In com­bi­na­tion with Revlimid and dexamethasone ^[11] (Decadron), Dr. Anderson was most ex­cited about the addi­tion of the anti­body elotuzumab ^[12].  He said that this com­bi­na­tion has achieved a very high re­sponse rate in myeloma patients.

Personalized Therapy

In the next sev­er­al years, Dr. Anderson thinks that personalized ther­apy for mul­ti­ple myeloma patients will be­come more and more common.

He ex­plained that myeloma patients can be treated dif­fer­en­tly based on their ge­netic profile.  However, he said, “We first need to be better able to profile patients to de­ter­mine who is likely to respond to which treat­ment; and sec­ondly, personalized med­i­cine in myeloma will re­quire us to de­vel­op more targeted ther­a­pies.”

If ad­vances are made in these two areas, Dr. Anderson said, “I would think over the next three to five years that personalized treat­ments will oc­cur.”

Myeloma Stem Cells

In the com­ing years, myeloma spe­cialists also hope to better under­stand myeloma stem cells, the can­cer­ous cells that reproduce and may be responsible for relapse of the dis­ease.

“So far, we have not been able to reproducibly identify that stem cell, but there is great emphasis on trying to under­stand its biology so we can ef­fec­tively target it,” said Dr. Anderson.  “Ultimately, in order for cure to oc­cur, the ability for myeloma to return and cause relapse will have to be over­come.”

Cure For Myeloma

Many myeloma spe­cialists differ in opinion about the goal of treating mul­ti­ple myeloma patients.

For some, the goal is to cure myeloma patients by achieving and main­taining a com­plete re­sponse or elim­i­nat­ing all traces of myeloma.  Others argue that the aggressive treat­ment needed to nearly wipe out the myeloma cells can severely im­pact a patient’s quality of life, and yet the patient is still likely to relapse.  Many of these physicians would prefer to get the dis­ease to a safe level and then treat to con­trol the dis­ease while main­taining a high quality of life for the patient.

When asked his opinion in the debate, Dr. Anderson replied, “Absolutely, the goal should be to cure our patients.”

“I strongly think that in the era of novel ther­a­pies, used in com­bi­na­tion and as main­te­nance, sustained com­plete re­sponses will be achievable in the majority of patients,” said Dr. Anderson. “First achieving com­plete re­sponses and then sustaining those com­plete re­sponses is, in fact, the path­way to­wards cure, and I do think we’re closer to that goal than ever before.”

Dr. Anderson said that this ap­proach does not have to sig­nif­i­cantly im­pact quality of life.  “Quality of life is obviously paramount and of the highest importance,” he said. “The good news is that novel ther­a­pies used appro­pri­ately really are also very well tol­er­ated.”

“I don’t think it needs to be one or the other.  I think we can actually achieve high re­sponse rates, and fortunately, they are asso­ci­ated not only with living longer, but living longer with a quality life,” he added.

Advancing Re­search Through Clinical Trials

Dr. Anderson said that the quickest way for ad­vances to be made in the treat­ment of myeloma is for patients to par­tic­i­pate in clin­i­cal trials.  “I would most enthusiastically urge patients to endorse the concept of clin­i­cal trials and ask patients to par­tic­i­pate whenever possible.”

He said patients should par­tic­i­pate because “you will get top notch, cutting edge, novel treat­ments that will give you the best possible chance for doing well in myeloma.”

For those who are con­cerned about ran­domized clin­i­cal trials, in which half of the patients re­ceive the standard of care instead of the study drug, Dr. Anderson said, “We don’t know which of the op­tions are better.  Usually in a ran­domized trial, there is the oppor­tu­ni­ty later on to re­ceive the treat­ment that you were not chosen to re­ceive if it in fact is beneficial.  In other words, a patient often ends up re­ceiv­ing the new med­i­cine either right away or later.”

Dr. Anderson concluded by saying, “I think it’s a very ex­cit­ing time in myeloma, and it’s a unique privilege for all of us to help, to­geth­er with our patients, im­prove the out­come in this dis­ease.”

For more in­­for­ma­tion about Dr. Anderson’s ap­proach to treating mul­ti­ple myeloma, please see part one ^[1] of this series.