NCI-CCC Myeloma Tumor Board Question&nbsp;&nbsp;&nbsp;

What is your current practice for de-escalation of frequency of administration of bispecific antibodies among responders in patients with relapsed/refractory multiple myeloma?

How do you approach pelvic radiation therapy for a patient with multiple myeloma who needs more intensive therapy (e.g., Dara-KRd or impending CAR-T) with a risk of cytopenias?

For example, a large iliac or sacral plasmacytoma causing symptoms. Both medical oncologists and radiation oncologists get nervous about RT-related cy...

How often do you assess for frailty in your clinical practice for patients with Multiple Myeloma and what tool do you use?

For example: eyeball test, simplified frailty assessment (Facon et al.), IMWG frailty score, ECOG only?

How do you approach treatment for patients with proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) with end-stage renal disease who are considering kidney transplant?

Most patients with PGNMID have no detectable disease in their marrow or blood and urine protein cannot adequately be monitored.

What is your preferred approach to a patient with myeloma who has refractory disease to Dara-VRd in the frontline setting?

How are you dosing IVIG following BCMA CAR-T or bispecific antibodies in multiple myeloma?

Do you only offer it for patients with a documented IgG < 400? Do you check the IgG at all, or are you doing primary prophylaxis?

How do you approach initial treatment for AL amyloidosis with excess plasmacytosis in the bone marrow, that has cardiac involvement and is not a transplant candidate?

Let's assume they have cardiac involvement and transplant may not be feasible.

How would you approach dose modifications and/or frequency of lenalidomide in patients with advanced renal impairment (eGFR <30)?

The FDA package insert suggests 2.5 mg daily in these settings, while the PrE1003 study demonstrated that a higher dose is feasible. Many oncologists ...

What is your approach to determining fitness for patients to undergo CAR-T therapy for relapsed/refractory multiple myeloma, and any absolute perceived contraindications for CAR-T?

In what scenarios (if ever) would you check peripheral blood flow cytometry in a patient with known multiple myeloma to evaluate for circulating plasma cells (CPCs) in the absence of an abnormal smear?

There are some retrospective data that CPCs are associated with worsened outcomes after transplantation. Anecdotally, CPCs could be collected as part ...

Based on the DREAMM-7 and DREAMM-8 data, if approved again in the US, how would you incorporate belantamab mafadotin in your practice?

Based on the IMROZ and BENEFIT data, would you recommend quadruplet therapy for non transplant eligible newly diagnosed multiple myeloma?

In 2024, do you consider isolated gain(1q) [not amp(1q)] to be a high-risk cytogenetic abnormality in multiple myeloma?

Most would argue that gain(1q) in combination with another high-risk feature constitutes ultra-high-risk multiple myeloma, and most would argue (with ...

How long should we treat patients with newly diagnosed myeloma with bisphosphonates or RANKL inhibitors for their myeloma bone disease given recent data?

The OS benefit with Zometa was seen only in patients with myeloma bone disease achieving less than or equal to a partial response. SRE risk reduction ...

Is there any value to getting a bone marrow biopsy at the time of biochemical relapse in multiple myeloma before switching to a new line of therapy?

For many clinical trials, a screening bone marrow biopsy is necessary to get a new baseline. Do you do the same in real-world practice?

Do you resume zoledronic acid or denosumab at relapse in multiple myeloma?

Previous questions have focused on the newly diagnosed setting and choice of bisphosphonate versus denosumab. IMWG guidelines do recommend resuming zo...

In the current myeloma landscape, do you make treatment decisions based on MRD results, either for MRD negativity or MRD resurgence?

With the recent ODAC review of the commerically available CAR-T therapies in relapsed/refractory myeloma post 1-3 lines of therapy, what is your preferred regimen/therapy for first relapse, and which are the situations where you would absolutely consider CAR-T therapy at first relpase?

For patients on commercial teclistamab who achieve a response, are there patient-specific or response-specific parameters that would prompt you to de-escalate therapy from once per week?

For example - minimum number of months of therapy, driving distance to clinic, at least a CR with or without MRD negativity?

For a Jehovah's Witness patient with multiple myeloma, could you safely offer a BCMA-directed bispecific antibody or CAR-T therapy?

Please assume that IVIG is fine (as it is for many Jehovah's Witness patients, since IgG is often not considered a blood product per se).

Are there any circumstances where you recommend early institution of systemic therapy for patients with solitary plasmacytoma?

Specifically, do you offer closer follow-up for certain patients after local radiation?

How do you approach the initial dosing of carfilzomib for patients with relapsed multiple myeloma?

Is the therapeutic purpose of the proteasome inhibitor to maximize total dosage per week or number of infusions per week?

How extensive of a workup do you do for systemic AL amyloidosis for a patient with a resected amyloidoma, localized AL amyloid deposition in their airway or lungs, who has no other symptoms?

Would you do a 24-hour urine and echocardiogram in all of these patients? Cardiac biomarkers, PT/PTT, or any other such blood tests?

For a patient with triple-class-refractory myeloma and cytopenias who has been collected for CAR-T, would you choose aggressive chemotherapy or a bispecific antibody for bridging?

This question seems quite specific but happens quite often. Multi-drug chemotherapy runs the risk of profound cytopenias and infections, while bispeci...

With the CANOVA results in mind, would you continue using venetoclax in patients with multiple myeloma with t(11;14)?

What is your approach to mitigating the infection risk with bispecific antibodies in multiple myeloma?

4 Answers available

How do you choose between the different recently approved Bispecifics Antibodies for Relapsed/Refractory Multiple Myeloma?

I.e. dosing regimen frequency, side effect profile, duration of follow up, etc.

For patients who require aggressive debulking in multiple myeloma, what is your preferred chemotherapy regimen and why?

Modified HyperCVAD? V(R)D-PACE? DCEP? Are there any data to favor one over the other?

How do you manage IgM related peripheral neuropathy?

Do you utilize rituximab or any other specific management strategies?

How would you approach BCMA-directed therapy in a patient with myeloma and renal failure on dialysis?

Would you prefer CAR-T or bi-specific or neither? If CAR-T, how do you approach lymphodepletion?

How do you approach post-transplant maintenance for patients with high-risk myeloma?

Which PI and at what dosing intervals? Dexamethasone or not? Emory has now published data with VRd consolidation as well as KPd consolidation, while ...

Do you recommend routinely getting periodic 24-hour urine monoclonal protein study for patients with active multiple myeloma?

If so, why?

4 Answers available

Would you implement CAR-T therapy earlier in practice if approved in earlier lines for multiple myeloma based on the KarMMa-3 and CARTITUTUDE-4 studies?

Do you always start treatment for patients who meet diagnostic criteria for multiple myeloma by SLiM criteria alone?

i.e., 60+% bone marrow plasmacytosis, light chain ratio >100, and/or >1 MRI lesion

Do you change treatment for confirmed biochemical progression in patients with otherwise secretory MM even if the M-spike is <0.5 g/dL?

Is there still a role for plasma exchange/PLEX for confirmed or suspected cast nephropathy in multiple myeloma to rapidly reduce light chain burden?

In addition to reversing hypercalcemia, initiating myeloma therapy, etc.

Assuming all options for BCMA-directed therapy are available, how would you approach treatment for a patient with 4 prior lines of myeloma-directed therapy who is eligible for a BCMA-directed therapy?

Ide-cel? Cilta-cel? Teclistamab?

For patients with IgG kappa multiple myeloma receiving an IgG kappa mAb (i.e., daratumumab), how important is it clinically to use an interference assay if they're in a VGPR to see if their M-spike might actually be 0?

For example, would you use a tool like the Hydrashift assay? Would this change your management?

When you use selinexor for relapsed/refractory myeloma, with what total weekly dose do you practically start?

If tolerated through Cycle #1, how aggressively do you try to titrate the selinexor dose up toward 100mg weekly or 80mg twice-weekly? And does your a...

What is your approach for using anticoagulation/aspirin in patients with multiple myeloma?

What is your preferred up-front treatment for transplant-eligible patients with primary (de novo) plasma cell leukemia?

What is your approach to pRBC transfusion support for myeloma-related anemia?

How much weight do you give to a hgb/hct threshold versus symptoms?

What are your takeaways from the GPRC5D-Targeted CAR-T trial (Mailankody et al. NEJM Sept 2022) and any key differences compared to the BCMA directed products?

If you treat a patient with high-risk smoldering myeloma on trial and they develop biochemical progression by M-spike, but still no CRAB-SLiM criteria, what would you do next?

In this case, the patient had received daratumumab/lenalidomide/dexamethasone as part of a cooperative group trial. Would you say that the patient had...

Is there a role for repeat CAR-T with a potentially different product in relapsed and refractory multiple myeloma?

Do you perform a periodic PET CT to screen for extramedullary disease in patients with MM who are in remission?

Where does Elotuzumab-based combination therapy, specifically EPd, fit in your treatment paradigm for relapsed MM?

Does sequence matter?

What induction regimen would you choose for a patient with newly diagnosed multiple myeloma with incidental amyloidosis noted on bone marrow biopsy, but with no end-organ damage as a result of amyloid deposition?

Would you consider Dara-CyBorD or a MM triplet/quadruplet such as VRd or Dara-VRd?

4 Answers available

How do you approach treatment for a patient with a biochemical relapse while on maintenance lenalidomide after autologous stem cell transplant for multiple myeloma?

What factors (i.e. timing from transplant, dose, prior therapy) impact your decision?

How do you approach the decision to pursue early versus delayed autologous stem cell transplantation in newly diagnosed multiple myeloma?

How would you approach therapy for a patient with smoldering multiple myeloma whose light chain ratio has increased to greater than 100 over several years in the absence of any other myeloma-defining events?

Does a progressing kappa/lambda ratio > 100 at any point in time warrant treatment, or does one wait to treat patients in the setting of a slowly i...

For relapsed/refractory myeloma, how long of a disease-free interval from first autologous transplant do you recommend before considering a second autologous transplant?

For patients with mild CKD, how do you decide between zoledronic acid and denosumab for bone protection in patients with multiple myeloma?

For pts w/ eGFR between 30-60

What is your experience with using Frailty Index or other geriatric screening in making decisions for elderly patients with multiple myeloma?

Frailty Index per Palumbo et al. PMID 25628469Is it practical to apply in clinics? Have you made decision changes based on it?

In what clinical scenarios do you utilize venetoclax-based therapy in relapsed/refractory multiple myeloma?

Venetoclax has demonstrated efficacy in patients harboring t(11;14) mutations but is not FDA approved for MM. Can you expand on what situations you ma...

How do you approach patients with recurrent grade 3+ neutropenia on IMiD-containing regimens (e.g., VRd or KRd) beyond dose reductions?

For example: shorten IMiD duration each cycle, add scheduled G-CSF, add antibacterial prophylaxis, etc.

What infectious prophylaxis do you use for patients with newly diagnosed multiple myeloma?

How do you decide how long to continue?

What is your treatment of choice for triple class refractory multiple myeloma?

CAR-T (any specific preference of product?) vs bispecific antibodies vs any other specific agents not previously utilized?

How does one interpret persistently positive lambda light chains on serum immunofixation but without measurable serum monoclonal protein and a normal light chains and ratio?

Is a repeatedly abnormal serum immunofixation all it takes for MGUS?

Which patients with smoldering myeloma do you treat?

How would one alter therapy in a transplant-ineligible AL amyloidosis with less than a complete response to six cycles of Dara-CyBorD?

Would you continue with daratumumab maintenance per ANDROMEDA or switch regimen?

What is the optimal prophylaxis regimen to use prior to a selinexor based regimen in the treatment of multiple myeloma for nausea and electrolyte abnormalities?

How do you approach a patient with an anaplastic plasmacytoma without systemic evidence of disease in the bone marrow?

What about multiple anaplastic plasmacytoma without bone marrow involvement?

Do you continue bortezomib past 8 cycles for transplant ineligible patients with multiple myeloma on VRd who are tolerating therapy well with no neuropathy?

Would you use MRD status to guide your decision making?

Would you move to a venetoclax-based regimen for a patient with pentarefractory MM and t(11;14) translocation, previously treated with bortezomib and carfilzomib?

If so, venetoclax/dexamethasone by itself or do you include a PI?

What is your preferred maintenance strategy for high risk multiple myeloma?