I have a red-headed friend with lym­phoma. She seems to be an outlier on the spectrum of “average responses” to treat­ment. Even common front­line drugs have caused her unexpected side effects. When it comes to her treat­ment, she teases her specialists that she’s a “medical uni­corn,” some­thing never before seen. I’m beginning to think she’s not the only one.

I am writing this column on Day +11, or the eleventh day after my husband Daniel’s au­tol­o­gous stem cell trans­plant. The road we took to get here did not go accord­ing to plan. He’s been hospitalized numerous times, ex­peri­enced failed treat­ments, and we’ve had to make some tough deci­sions about clin­i­cal trials. We don’t yet know if the journey has been a success, but we’ve doubled down for a positive out­come and given it all we’ve got.

Daniel started treat­ment for his multiple myeloma in April. After discussing treat­ment options with his specialist, we determined that Daniel would receive three to four cycles of induction ther­apy followed by stem cell collection, an au­tol­o­gous stem cell trans­plant, and then main­te­nance ther­apy for an indefinite amount of time thereafter.

Daniel’s risk markers had pre­vi­ously indicated that his myeloma was “average risk,” with a t(11:14) chromosomal ab­nor­mal­ity and 20 per­cent myeloma involvement on his last bone marrow aspirate. Given his risk level, Daniel’s trans­plant specialist believed he was a good can­di­date for achieving a com­plete remission, and suggested that his stem cell trans­plant plan would likely involve only mel­phalan, the standard ap­proach used in trans­plants for multiple myeloma.

Daniel only had one bone lesion on his clavicle, and other­wise he is healthy and young, so we were told that we might even be able to do his entire stem cell trans­plant process outpatient. This meant that he could recover at home after the mel­phalan admin­istra­tion, and we would return to the hospital several times a week for labs and fast-track clinic checks until such time that his specialist released him to return to work.

It’s amazing how quickly things can change when you have multiple myeloma.

Daniel’s induction ther­apy consisted of Kyprolis (car­filz­o­mib), Revlimid (lena­lido­mide), and dexa­meth­a­sone. The first cycle was promising. It dropped his M-spike from 3.1 g/dL to 1.8 g/dL (31 g/l to 18 g/l). This drop in M-spike was enough to qualify as a partial response, and he therefore met our treat­ment center's qualifications for a stem cell trans­plant. We met with his trans­plant specialist and began planning for Daniel's trans­plant.

By the end of cycle 2, the optimism began to become more measured as the first setback occurred. During cycle 2, Daniel was hospitalized for painful kidney stones. Without any history of kidney issues or kidney stones in particular, we had to assume that he was experiencing a pre­vi­ously unreported / unseen reac­tion to one of the drugs in his treat­ment plan. It was a painful reminder that myeloma treat­ment is not an exact science. By the end of cycle 2, his M-spike had only decreased to 1.3 g/dL. The team hoped that he would achieve a deeper response by the end of cycle 3.

We then ex­peri­enced another setback. The Revlimid had given Daniel bilateral pul­mo­nary emboli, or blood clots in both his lungs. Another hospital stay came and went, during which his doctors were able to stabilize his con­di­tion with ongoing Lovenox (enoxaparin) injections.

After a week’s delay, we proceeded with cycle 4 of Kyprolis and dexa­meth­a­sone alone, without the Revlimid. Sadly, we would soon learn that it was the Revlimid that seemed to be the pri­mary agent work­ing against Daniel’s myeloma. Once the Revlimid was removed, Daniel’s M-spike rose back up to 1.7 g/dL, and he became severely neu­tro­penic. Daniel’s M-spike would eventually rise to above 2.0 g/dL after cycle 4, and his free light chains were sporadic as well.

During this time, Daniel was restaged with another bone marrow aspiration, and we learned that his bone marrow plasma cell per­cent­age had increased from 20 per­cent to an esti­mated 30 to 40 per­cent. Imaging tests also indicated myeloma-related activity in his spine. With this level of marrow involvement and the increase in the M-spike above Daniel's initial partial response, the mood of his medical team changed sig­nif­i­cantly.

Not only did his induction ther­apy not bring about the com­plete response we had hoped to reach prior to the stem cell trans­plant, but it would seem that Daniel had re­lapsed before the trans­plant had even begun. This was not the response anyone ex­pec­ted from his “average risk” myeloma.

Due to his biochemical pro­gres­sion, we had an extensive discussion about strategy. Since Daniel no longer was in remission of any kind, he no longer qualified for a stem cell trans­plant. So we decided to proceed with what his doctors called “salvage ther­apy.”

We were presented with two options.

Option one would be to proceed with an immuno­therapy-based regi­men con­taining Darzalex (dara­tu­mu­mab) and then see if Daniel could qualify for a trans­plant thereafter.

Option two would be to undergo a chemo-mobilization regi­men designed to both treat his myeloma and increase his white blood cell counts. Assuming that he didn’t develop any com­pli­ca­tions, Daniel would then go im­medi­ately for stem cell collection, followed by the trans­plant.

After extensive conversation about these options, we decided not to burn through a line of immuno­therapy and instead utilize the harsher chemo-mobilization option in hopes that it would have enough of an impact on his multiple myeloma to allow for both stem cell collection and the trans­plant.

The chemotherapy / mobilization regi­men Daniel received is called "CBAD," an acronym that reflects the cyclophosphamide (Cytoxan), bor­tez­o­mib (Velcade), Adriamycin (doxorubicin), and dexa­meth­a­sone in­cluded in the regi­men. Due to the toxicity of the four-drug com­bi­na­tion, Daniel had to be hospitalized for its admin­istra­tion and treat­ment of the side effects.

The side effects were everything you would ex­pec­t from high-dose chemotherapy. Daniel began to lose his hair, and he had nausea and diarrhea. We felt the side effects would be worth it, though, if the regi­men would get us to com­plete remission prior to the stem cell collection.

Unfortunately, Daniel’s myeloma once again did not respond according to plan.

After CBAD, Daniel’s M-spike increased from 1.7 g/dL to 2.2 g/dL. It was a shocking out­come, and we worked with Daniel’s trans­plant specialist to determine the best way to do Daniel's stem cell trans­plant given how he had responded to the CBAD regi­men.

Then, another delay. Daniel was hospitalized for an unexplained fainting episode that happened when he was giving blood at the stem cell clinic lab, and then later on for headaches and an in­fec­tion related to a recurring sinus in­fec­tion.

After his fifth hospi­tal­iza­tion in as few as five months, Daniel went for stem cell collection. Over two days of Neupogen (filgrastim) infusions and stem cell harvesting, Daniel was unable to produce enough stem cells, so nightly two-hour Mozobil (plerixafor) infusions were added to the daily four-hour Neupogen infusions.

This was a trying time because the infusions had to be admin­istered exactly 12 hours apart from one another. That meant long days and nights at the cancer center with brief trips home to sleep, only to start the process all over again the next day. This went on for three more days, until the stem cell collection process was com­plete.

In the end, enough cells were collected for Daniel to have two au­tol­o­gous stem cell trans­plants. But what kind of au­tol­o­gous stem cell trans­plant would be best for him? In no way had he responded to his treat­ments thus far the way an “average risk” myeloma patient should.

For reasons we could not explain, Daniel was not average risk after all. He was a myeloma unicorn.

Over the next week, we spoke with different members of Daniel’s stem cell trans­plant team. We knew that they no longer con­sidered him a good can­di­date for the standard high-dose chemotherapy regi­men used during au­tol­o­gous stem cell trans­plants. What we didn’t know was just how difficult the alter­na­tive would be.

Daniel always says that the news is never as good or as bad as you think it’s going to be when you have multiple myeloma. When I think back on our lives over the past six months, those words ring very true for me. I would add that the news is almost always unexpected as well.

In my next column, I’ll report on Daniel's trans­plant and the aggressive strategy his doctors recom­mended for it.