Patient Case 3: A 65-Year-Old Woman With Relapsed Multiple Myeloma
After reviewing their third patient case, expert hematologist-oncologists highlight the treatment armamentarium for relapsed/refractory multiple myeloma.
Transcript:
Sundar Jagannath, MD: Dr Richter, would you present your case of relapsed and refractory myeloma and how you managed it?
Joshua Richter, MD: Absolutely. This is a case of a 65-year-old [woman] with IgA [immunoglobulin A] lambda plus lambda multiple myeloma. She was originally diagnosed in 2011 with Durie-Salmon stage IIIA disease, a normal karyotype. She began her induction therapy with bortezomib and dexamethasone, which was later enhanced to VCD [bortezomib, cyclophosphamide and dexamethasone], where she achieved a VGPR [very good partial response]. This was followed by VRD [bortezomib, lenalidomide and dexamethasone] and, ultimately, a stem cell transplant in June 2012. She then went on to lenalidomide maintenance from November 2012 to March 2014, when, unfortunately, she began to have a number of relapses. She subsequently went on to therapies with VRD, followed by panobinostat with Len-Dex [lenalidomide and dexamethasone], followed by Dara-Pom-Dex [daratumumab plus pomalidomide and dexamethasone], followed by carfilzomib and ibrutinib, and then selinexor. At [this] point, in 2017, she required debulking with VD [bortezomib and dexamethasone] set and had a salvage autologous transplant with carmustine and melphalan. This was followed by pazopanib maintenance on a clinical study. Unfortunately, she relapsed from this in 2018. At that time she was deemed eligible for one of our clinical trials with a BCMA [B-cell maturation antigen]–targeting bispecific antibody. She received her bispecific antibody and completed her cycle 1 day 1 infusion at 13:25. At the time, her baseline vital signs were stable, with a blood pressure of 132/69 [mm Hg], heart rate of 80 [beats/min], SpO2 [oxygen saturation] 99% on room air, [and] ICE [Immune Effector Cell–Associated Encephalopathy] score of 10/10. Her inflammatory markers—CRP [C-reactive protein] and ferritin—were within normal limits at 5.1 [mg/L] and 42 [ng/mL], respectively, and the patient was without complaints. Approximately 9 to 10 hours later, at 22:05, she had a low-grade temperature of 100.2 °F, blood pressure maintained at 130/70 [mm Hg], heart rate of 93 [beats/min], SpO2 98% on room air, [and] still with an ICE of 10/10. The patient reported feeling a little warm, but otherwise without complaints. However, about an hour and a half later, at 23:44, her temperature rose to 102.1 °F, [her] blood pressure was a little bit lower at 102/55 [mm Hg], she was tachycardic at 118 [beats/min], SpO2 94% on room air, and still with an ICE of 10/10, but at this time she felt warm and began having mild rigors, and inflammatory markers were somewhat elevated, with a CRP of 30.7 [mg/L] and ferritin of 69 [ng/mL]. At this time we determined that she was having cytokine release syndrome [CRS] that warranted intervention. We administered tocilizumab at 8 mg/kg, acetaminophen 1000 mg, and intravenous fluid. Following this, on cycle 1 day 2 at 2:30 am, her temperature had gone back down to 97.8 °F, [her] blood pressure was somewhat improved at 116/72 [mm Hg], heart rate of 96 [beats/min], SpO2 98% on room air, [and] ICE 10/10, and the patient reported feeling clinically better and was without complaint. Subsequent inflammatory markers later that day showed a CRP slightly downtrending at 21.6 [mg/L] and ferritin of 67 [ng/mL]. The patient was ultimately discharged from the hospital on cycle 1 day 4 without subsequent manifestations of CRS. The patient went on to achieve a stringent complete remission on clinical study; however, after 14 months she ended up having relapsed disease and was placed on alternative therapy.
Sundar Jagannath, MD: That is a very interesting case. Could you describe how the bispecific antibodies work? Then we’ll follow up with the CRS mechanism and management.
Joshua Richter, MD: Absolutely. I am a huge fan of bispecific antibodies because they are off-the-shelf. We recognize our immune system is 1 of the best cancer fighters, and bispecifics enhance that. And we’re all familiar with monoclonal antibodies like rituximab and daratumumab; 1 arm grabs onto the cancer cell and tries to kill it. But bispecifics have 2 arms; 1 arm grabs onto the cancer cell, the other grabs onto our own T cells and activates them to attack the cancer. [It’s a] kind of “myeloma Thunderdome,” where you get the T cell and myeloma cell in 1 room. Two enter but only 1 leaves, and that’s hopefully the triumphant T cell. This is really great at upregulating our body’s immune system and inflammatory markers to engender cell killing.
Sundar Jagannath, MD: This brings me back to CAR [chimeric antigen receptor] T cells. Dr Richard, you also get a cytokine storm following CAR T-cell therapy. I saw in this particular patient she developed CRS. Roughly, she got it around 11:30 am and finished the infusion, but ran into trouble 12 hours later around 11:00 pm, and you managed her CRS with toci [tocilizumab].Can you tell me in the CAR T situation how the CRS is and how is the management there?
Shambavi Richard, MD: Interestingly, for CAR T [-cell therapies], because there are so many different products out there, the timing of the CRS is very product specific, first of all. We now have 2 commercially approved [CAR-T] products. In the case of ide-cel [idecabtagene vicleucel], we actually start seeing CRS on the first day post infusion, whereas with cilta-cel [ciltacabtagene autoleucel], we see it at a median of approximately 7 days. So, the timing is very different. Secondly, when you compare bispecifics and CAR Ts, the frequency of CRS is generally greater with CAR Ts; also, the severity may be a little [higher] with CAR Ts as opposed to bispecifics. So, the timing is different, frequency is different, and severity is different; but essentially, CRS is CRS. Management [starts when the patient develops a] fever, which we call grade 1 CRS; just the fever and not too much else going on. I tend to start giving the toci sooner rather than later because we want to do a couple of things. We want to ward off worsening CRS, and we want to also, hopefully, mitigate the risk of subsequent neurotoxicity and things like that. So, [those are], in general, some of the differences in CRS between CAR T and bispecifics.
Sundar Jagannath, MD: If I’m hearing you correctly, the CRS with CAR T is more intense. And CAR T-cell therapy is usually selected for fitter patients [awaiting] transplant [who are] somewhat more robust, physically and cardiovascularly. But, if I understand the 2 of you, you would be much more willing to give a bispecific antibody to an older gentleman, [say,] 80 years old, and [would] choose CAR T for a 60-year-old. Is that a fair statement?
Shambavi Richard, MD: In general, I would say that is fair. Certainly, we’ve done CAR T [therapy] for older patients. Some of the things we’ve seen, if the disease is rapidly progressive or [if there is a] large disease burden we are unable to get down, it might be a little bit safer to do a bispecific antibody than to do a CAR T. On the other hand, [for] younger, fitter patients, [because] the disease has been pretty refractory to a lot of other treatments, CAR T is a good option. But the disease can be controlled to some extent, so you are not an extremist when you are coming in for the CAR T. I think those are the patients [for whom] you may prefer a CAR T to a bispecific.
Transcript edited for clarity.
The Hidden Danger Unveiling the Connection Between Multiple Myeloma and Pleural Effusion
This case highlights the importance of early recognition and management of pleural effusion in patients with multiple myeloma and underscores the need for further research into optimal management strategies and underlying mechanisms.
