Physicians in the United States are able to prescribe Kyprolis for their patients now that the drug has been approved for the treat­ment of multiple myeloma.

The drug's widespread availability, however, raises the important question: For what types of myeloma patients are physicians likely to prescribe Kyprolis?

Last month, the U.S. Food and Drug Administration (FDA) approved Kyprolis ^[1] (car­filz­o­mib) for the treat­ment of multiple myeloma patients meeting specific criteria. The patients must have received at least two prior ther­a­pies, including Velcade ^[2] (bor­tez­o­mib) and an immuno­modu­la­tory agent, meaning either Revlimid ^[3] (lena­lido­mide), thalidomide ^[4] (Thalomid), or pomalidomide ^[5].  The patients must also have dem­onstrated disease pro­gres­sion on or within 60 days of completing their last ther­apy.

For more in­­for­ma­tion, see the related Beacon news article announcing the FDA approval ^[6] as well as a Q&A ^[7] about the approval.

Although Kyprolis has been approved by the FDA for this specific set of myeloma patients, once a drug is approved in the U.S., physicians have substantial freedom to prescribe the drug as they deem appropriate.

At the same time, Medicare, Medicaid, and private insurance com­pa­nies may decide to control health care costs by restricting reim­burse­ment of Kyprolis treat­ment to patients meeting the FDA criteria described above.  This may particularly be the case with Kyprolis, given that it is cur­rently the most expensive myeloma treat­ment available.

So, for which patients are myeloma specialists likely to prescribe Kyprolis?

To gain a better sense of what the answer to this question is likely to be, The Beacon conducted an informal survey with a wide range of myeloma specialists around the country.  We asked each of them: "How do you see yourself using Kyprolis in the near future – e.g., for what kinds of patients?"

Below is what the myeloma specialists told us.

Please note that some of the comments have been edited for brevity and clarity.  For consistency, comments also have been edited to refer to patent-protected drugs by their brand names.

Amrita Krishnan, City of Hope:

We would use Kyprolis for patients with re­lapsed myeloma. We are also going to be exploring its use in the post-transplant setting as consolidation in a clinical trial.

We have par­tic­i­pated in several of the Kyprolis earlier trials and are very pleased about its approval as our experience with it in clinical trials has been favorable.

Ruben Niesvizky, Weill Cornell Medical College:

We are using Kyprolis upfront (first-line) in our flagship protocol ‘Car-BiRd ^[8],’ [which is a Phase 2 clinical trial that will evaluate treat­ment of newly diagnosed myeloma patients with Kyprolis and dexa­meth­a­sone followed by treat­ment with clarithromycin ^[9] (Biaxin), Revlimid, and dexamethasone ^[10] (Decadron), and finally Revlimid alone.]

In addi­tion, Kyprolis would be an excellent choice for patients who are intolerant to Velcade by virtue of their neu­rop­athy [pain, tingling, or loss of sensation in the extremities].

Patients who have suffered pro­gres­sion of disease after at least three lines of ther­apy including Velcade, immuno­modu­la­tory drugs, and alkylators will also benefit.

Philip McCarthy, Roswell Park Cancer Institute:

[I see myself using Kyprolis] as part of salvage ther­apy, especially for patients who have re­lapsed or progressing disease after Velcade-containing regi­mens.  I would expect to recommend use in com­bi­na­tion with Revlimid and dexa­meth­a­sone for this patient population.

Guido Tricot, University of Iowa Hospitals and Clinics:

The availability of Kyprolis will make it possible to provide a proteasome inhibitor to those patients who do not tolerate Velcade because of neu­rop­athy.

Proteasome inhibitors are probably the most potent anti-myeloma agents given as single ther­apy, with the exception of high-dose melphalan ^[11] [Alkeran].

It remains to be shown that Kyprolis is equally potent as Velcade. If that is the case, it may replace Velcade as the preferred proteasome inhibitor.

Jeffrey Wolf, University of California, San Francisco:

The FDA has approved Kyprolis for patients who have had at least two prior regi­mens which are not now work­ing, and I think that is entirely appropriate.  In general that will include patients who have already had Revlimid and Velcade.

Frederic Reu, Cleveland Clinic:

At this point, we will use Kyprolis predominantly for re­lapsed or refractory patients and patients with neu­rop­athy in any of the schedules that have been found safe.

Ravi Vij, Washington University in St. Louis:

In the im­medi­ate future, I will be using Kyprolis in patients with re­lapsed and refractory multiple myeloma who have been exposed to Revlimid and Velcade and are needing alter­na­tive ther­a­pies.

Sergio Giralt, Memorial Sloan-Kettering Cancer Center:

[I see myself using Kyprolis for] patients with re­lapsed and refractory myeloma intolerant to Velcade or with neu­rop­athy, as part of com­bi­na­tion ther­apy for re­lapsed and refractory myeloma, and upfront for patients with neu­rop­athy.

Ken Shain, Moffitt Cancer Center:

Much of the excitement surrounding the use of this new agent [Kyprolis] is that we now have an addi­tional agent with which to treat our re­lapsed and refractory patients.

Kyprolis has been approved as a single agent in re­lapsed/refractory multiple myeloma and should cur­rently be used only in this setting.  However, there are ongoing clinical trials both in the re­lapsed/refractory and pre­vi­ously untreated patient settings in com­bi­na­tion with Revlimid, cyclophosphamide ^[12] [Cytoxan], and other agents that bear watching.

For instance, the Phase 2 study, PX-171-006 ^[13], which is examining the com­bi­na­tion CRd (Kyprolis, Revlimid, and low-dose dexa­meth­a­sone) in re­lapsed patients, has dem­onstrated very promising results.

Preliminary data [has also been presented] on the same com­bi­na­tion ^[14] in pre­vi­ously untreated patients.  These results suggest unprecedented disease control in the upfront setting.

However, all of these studies are early in analysis and devel­op­ment, and the results need to be validated prior to off-study utilization in these settings and com­bi­na­tions.

As these clinical trials mature, the use of Kyprolis will likely expand and be used in com­bi­na­tion with other thera­peutics.  To date, however, it should be used as approved.

Adam Cohen, Fox Chase Cancer Center:

In the near future I will likely be using Kyprolis in patients who have progressed after pre­vi­ous Velcade and Revlimid, or for those who are unable to tolerate Velcade due to neu­rop­athy or other reasons.

Eventually, I think we’ll be using it earlier in the disease course, and there is a proposed cooperative group trial comparing Kyprolis, Revlimid, and dexa­meth­a­sone versus Velcade, Revlimid, and dexa­meth­a­sone for newly diagnosed patients that will hopefully open in the next six months.  This will provide more data about using it in the front-line setting and about how it compares to Velcade head-to-head.

Seema Singhal, Northwestern University:

I expect to use [Kyprolis] in patients with re­lapsed disease. I have already had experience with enrollment of approx­i­mately 50 patients in clinical trials with Kyprolis.

Peter Voorhees, University of North Carolina at Chapel Hill:

The recent FDA approval of Kyprolis is an important step forward for patients with myeloma.

In the short term, Kyprolis is now an important option for those patients who have received at least two pre­vi­ous ther­a­pies for their myeloma (including Velcade and thalido­mide or Revlimid) and have re­lapsed disease that is resistant to the most recently used ther­apy.  This is the FDA indication as it stands now.

Patients who are particularly likely to benefit from Kyprolis are those with Velcade-sensitive disease who cannot tolerate Velcade due to periph­eral neu­rop­athy.  That being said, responses in Velcade-resistant disease are also seen.

Moving forward, ongoing studies will help pave the way for the use of Kyprolis in com­bi­na­tion ther­apy, both in the re­lapsed and newly diagnosed settings.

Vincent Rajkumar, Mayo Clinic:

We are testing Kyprolis in all stages of myeloma, including newly diagnosed disease and as part of pre-transplant con­di­tioning. We hope to activate an NCI cooperative group Phase 3 study in newly diagnosed myeloma this year in which all the major groups are expected to par­tic­i­pate.

Outside of trials, I would use it in patients who are refractory to Velcade- and Revlimid-containing regi­mens, consistent with the approved indication. In addi­tion, I would consider it in patients who are unable to tolerate Velcade and have pre­vi­ously failed other available options.

The Myeloma Beacon would like to thank the above physicians who par­tic­i­pated in the survey for their assistance and expertise.